Multi-resolution multi-object statistical shape models based on the locality assumption

Publication date: Available online 17 February 2017
Source:Medical Image Analysis
Author(s): Matthias Wilms, Heinz Handels, Jan Ehrhardt
Statistical shape models learned from a population of previously observed training shapes are nowadays widely used in medical image analysis to aid segmentation or classification. However, providing an appropriate and representative training population of preferably manual segmentations is typically either very labor-intensive or even impossible. Therefore, statistical shape models in practice frequently suffer from the high-dimension-low-sample-size (HDLSS) problem resulting in models with insufficient expressiveness.In this paper, a novel approach for learning representative multi-resolution multi-object statistical shape models from a small number of training samples that adequately model the variability of each individual object as well as their interrelations is presented. The method is based on the assumption of locality, which means that local shape variations have limited effects in distant areas and, therefore, can be modeled independently. This locality assumption is integrated into the standard statistical shape modeling framework by manipulating the sample covariance matrix (non-zero covariances between distant landmarks are set to zero). To allow for multi-object modeling, a method for computing distances between points located on different object shapes is proposed. Furthermore, different levels of locality are introduced by deriving a multi-resolution scheme, which is equipped with a method to combine variability information modeled at different levels into a single shape model. This combined representation of global and local variability in a single shape model allows the use of the classical active shape model strategy for model-based image segmentation.An extensive evaluation based on a public data base of 247 chest radiographs is performed to show the modeling and segmentation capabilities of the proposed approach in single- and multi-object HDLSS scenarios. The new approach is not only compared to the classical shape modeling method but also to three state-of-the-art shape modeling approaches specifically designed to cope with the HDLSS problem. The results show that the new approach significantly outperforms all other approaches in terms of generalization ability and model-based segmentation accuracy.

Graphical abstract

http://ift.tt/2l8sJV6

Visfatin correlates with hot flashes in postmenopausal women with metabolic syndrome: effects of genistein

Abstract

During menopause, an increased prevalence of metabolic syndrome (MetS) and central obesity seems to increase hot flashes (HFs). Visfatin is an inflammatory adipokine secreted by visceral fat. We investigated visfatin levels and its relationship with hot flash number and BMI, in postmenopausal women with MetS. We also evaluated the effect of genistein, an isoflavone effective in reducing HFs, on visfatin levels and HFs after 1 year of treatment. This was a randomized, double-blind, placebo-controlled trial. Postmenopausal women with MetS were randomly assigned to receive placebo (n = 60) or 54 mg genistein (n = 60), daily for 1 year. As main outcome measures, hot flashes number and circulating visfatin levels were evaluated. Visfatin significantly correlated with BMI and HFs number in women with MetS at basal. After 6 and 12 months, our results indicate a strong correlation and a significant effect of genistein in reducing both HFs and visfatin in women with MetS. The present study suggests that visfatin plays a role in the vasomotor symptoms, at least in postmenopausal women with metabolic syndrome. Genistein may reduce HFs decreasing the circulating levels of this inflammatory adipokine.

http://ift.tt/2ma5EiH

Thyroid hormone levels in the cerebrospinal fluid correlate with disease severity in euthyroid patients with Alzheimer’s disease

http://ift.tt/1UiB5nX

Chronic lymphocytic thyroiditis does not influence the risk of recurrence in patients with papillary thyroid carcinoma and excellent response to initial therapy

Abstract

Background

This study evaluated the recurrence in patients with papillary thyroid cancer and an excellent response to initial therapy, comparing those with and without chronic lymphocytic thyroiditis.

Methods

This was a prospective study. Patients who met the following criteria were selected: diagnosis of papillary thyroid cancer; submitted to total thyroidectomy followed or not by ablation with ¹³¹I; and neck ultrasonography without abnormalities, nonstimulated thyroglobulina (Tg) ≤0.2 ng/ml, and undetectable antithyroglobulin antibodies (TgAb) 12–18 months after initial therapy. The patients were divided into two groups: group A, with chronic lymphocytic thyroiditis on histology; group B, without chronic lymphocytic thyroiditis on histology.

Results

Groups A and B were similar in terms of sex and age of the patients, characteristics of the tumor, tumor-node-metastase stage and risk category. The time of follow-up ranged from 24 to 120 months (median 66 months). During follow-up, 5 patients of group A (2.6 %) and 9 patients of group B (2 %) developed recurrence (p = 0.77). Patients with chronic lymphocytic thyroiditis were more likely to progress to persistently borderline TgAb. No patient had positive TgAb (above the reference value) during follow-up. Recurrences occurred in 12/588 patients (2 %) with undetectable TgAb in all measurements, in 1/32 (3.1 %) with detectable TgAb on some occasion but that returned to undetectable spontaneously, and in 1/13 (7.7 %) with persistently borderline TgAb. These rates did not differ significantly (p = 0.25).

Conclusion

The results of the present study showed the absence of an association between chronic lymphocytic thyroiditis and recurrence risk at least in patients with an excellent response to initial therapy.

http://ift.tt/2lwMPJV

Pituitary magnetic resonance imaging in Cushing’s disease

Abstract

Adrenocorticotropin-secreting pituitary tumor represents about 10 % of pituitary adenomas and at the time of diagnosis most of them are microadenomas. Transsphenoidal surgery is the first-line treatment of Cushing's disease and accurate localization of the tumor within the gland is essential for selectively removing the lesion and preserving normal pituitary function. Magnetic resonance imaging is the best imaging modality for the detection of pituitary tumors, but adrenocorticotropin-secreting pituitary microadenomas are not correctly identified in 30–50 % of cases, because of their size, location, and enhancing characteristics. Several recent studies were performed with the purpose of better localizing the adrenocorticotropin-secreting microadenomas through the use in magnetic resonance imaging of specific sequences, reduced contrast medium dose and high-field technology. Therefore, an improved imaging technique for pituitary disease is mandatory in the suspect of Cushing's disease. The aims of this paper are to present an overview of pituitary magnetic resonance imaging in the diagnosis of Cushing's disease and to provide a magnetic resonance imaging protocol to be followed in case of suspicion adrenocorticotropin-secreting pituitary adenoma.

http://ift.tt/2magXXQ

Proopiomelanocortin, glucocorticoid, and CRH receptor expression in human ACTH-secreting pituitary adenomas

Abstract

ACTH-secreting pituitary tumors are by definition partially autonomous, i.e., secrete ACTH independent of physiological control. However, only few, small-sized studies on proopiomelanocortin (POMC) and its regulation by corticotropin-releasing hormone (CRH) or glucocorticoids are available. Objective of the present study was to report on constitutive and CRH- and dexamethasone-regulated POMC, CRH (CRH-R1), and glucocorticoid receptor (NR3C1) gene expression in a large series of human corticotrope adenomas. Fifty-three ACTH-secreting adenomas were incubated with 10 nM CRH or 10 nM dexamethasone for 24 h. POMC, CRH-R1, NR3C1, and its alpha and beta isoforms were quantified and medium ACTH measured. Constitutive POMC expression proved extremely variable, with macroadenomas exhibiting higher levels than microadenomas. POMC increased during CRH in most specimens; conversely, changes induced by dexamethasone were varied, ranging from decrease to paradoxical increase. No correlation between POMC and ACTH was detected in any experimental condition. CRH-R1 expression was not linked to the response to CRH while NR3C1 was expressed at greater levels in specimens who failed to inhibit during dexamethasone; glucocorticoid receptor α was the more abundant isoform and subject to down-regulation by dexamethasone. Our results demonstrate a considerable variability in POMC expression among tumors and no correlation between POMC and ACTH, suggesting that POMC peptide processing/transport plays a major role in modulating ACTH secretion. Further, CRH-R1 and NR3C1 expression were not linked to the expected ligand-induced outcome, indicating that receptor signaling rather than abundance determines corticotrope responses. Our findings pave the way to new avenues of research into Cushing's disease pathophysiology.

http://ift.tt/2lwBDwA

Selective determination of sulfonamides from environmental water based on magnetic surface molecularly imprinting technology

Abstract

In the study, a simple and selective method based on magnetic separation technology is presented for the extraction of sulfonamides (SAs) from environmental water, followed by liquid chromatography–tandem mass spectrometry. In this method, magnetic surface molecularly imprinted polymers (Fe₃O₄@SiO₂@MIPs) with super-paramagnetic property and high selectivity toward SAs were developed as magnetic adsorbents. The Fe₃O₄@SiO₂@MIPs were then applied to the selective extraction of SAs from environmental water. The extraction and enrichment were accomplished simultaneously in a single step by simply stirring the mixture of adsorbents and water samples. The Fe₃O₄@SiO₂@MIPs were characterized by scanning electron microscopy, Fourier-transform infrared spectrometry, and vibrating sample magnetometry. The adsorption thermodynamics and kinetics were employed to study the adsorption mechanism of the Fe₃O₄@SiO₂@MIPs. And the matrix effect of the method was evaluated. Calibration curves obtained by analyzing matrix-matched standards show excellent linear relationship (R = 0.9994–0.9999) in the concentration range of 10–1000 ng L⁻¹, and the limits of detection are in the range of 1.4–2.8 ng L⁻¹. The relative standard deviations of intra- and inter-day obtained are in the range of 2.8 to 7.8 and 3.1 to 7.9%, respectively. The proposed method was successfully applied to determine SAs in six environmental water samples, and SAs were detectable in four of them with the concentration from 10.5 to 120.2 ng L⁻¹.

http://ift.tt/2lxiydH

Factors affecting the variability in the observed levels of cadmium in blood and urine among former and current smokers aged 20-64 and ≥ 65years

Abstract

Data from National Health and Nutrition Examination Survey for 1999–2012 were used to evaluate factors that affect observed levels of blood cadmium (BCd) and urine cadmium (UCd) among former and current smokers aged 20–64 and ≥65 years. Adjusted levels (AGM) for BCd and UCd were higher among females as compared to males. The order of AGM for BCd by race/ethnicity for 20–64 years old was non-Hispanic white (NHW) < non-Hispanic black (NHB) and NHW > NHB for ≥65 years old. The order of AGMs for UCd for 20–64-year-old current smokers was NHW > NHB and NHW > NHB for former smokers. For 20–64-year-old current smokers, exposure to environmental tobacco smoke at home was associated with higher levels of BCd. Levels of both UCd and BCd increased with age, but the rate of increase was as much as seven times higher among ≥65 years old than 20–64 years old. For current smokers, the number of cigarettes smoked inside home was positively associated with the levels of BCd. For current smokers aged 20–64 years, the number of cigarettes smoked inside home was positively associated with the levels of UCd (p < 0.01), and the number of cigarettes smoked every day on the days they were smoked was also positively associated with the levels of UCd (p < 0.01). Among former smokers, levels of both UCd and BCd were positively associated (p < 0.1) with the number of cigarettes smoked per day at the time of quitting smoking and negatively associated with the time since smoking was quitted (p < 0.01).

http://ift.tt/2liLLXb

Baseline trace metals in Patella caerulea in a central Tyrrhenian ecosystem (Pontine Islands archipelago and Lazio region coastal sites, Italy)

Abstract

In this study, we tested the aptitude of the gastropod mollusk Patella caerulea as biomonitor of elemental pollution in seawater of a central Tyrrhenian ecosystem (Pontine Islands archipelago and Lazio region coastal sites, Italy). Concentrations of Cd, Cr, Cu, Ni, Pb, and Zn were measured in 120 individuals collected in six strategic locations in two sampling campaigns during 2011 and 2012. Samples of surrounding seawater were also collected in the same sites and tested for the same metals in order to obtain the respective concentration factors (CFs). Then, we analyzed the evolution of contamination in the selected sites and compared our results with the baseline levels (control charts) previously established for Tyrrhenian seas (Conti et al. Environ Sci Pollut R 22:3640–3651,2015). With this purpose, we defined six new variables (one for each metal) and then we applied multivariate statistics, i.e., cluster analysis and discriminant analysis on the principal component analysis factors in order to obtain more reliable results. Patella resulted to be a strong bioaccumulator of Cd (CFs = 8990) and a good accumulator of Cr, Pb, and Zn. The levels of the majority of metals (i.e., Cr, Cu, Ni, Pb, and Zn) in Patella decreased in the range from −13.06% of Zn to −42.51% of Ni in Fiumicino harbor, Anzio beach, and Ponza Harbor from 2011 to 2012. In general, the metal levels in these marine areas are low and within the previously established baseline ranges for Tyrrhenian Sea (control charts). Here, we found a not univocal trend of metal bioaccumulation patterns between the two sampling campaigns (2011–2012) in the selected sites. No one site resulted to be clearly more contaminated than another (i.e., harbor sites as expected). For instance, for Cd, we detected a relevant increase of its levels (+118%) in the harbors and Anzio beach sites from 2011 to 2012; however, they remained at lower levels of the lower limit (Q _2.5) of the control chart. Higher Pb levels with respect to the baseline values were observed for the majority of samples in the Ponza Cala Fonte site. Patella confirmed its usefulness as a cosmopolitan trace metal biomonitor in marine Mediterranean areas. The possibility of employing these results as a baseline level for comparative purposes in other marine areas is fully debated.

http://ift.tt/2lx8Qs3

Novel potential scaffold for periodontal tissue engineering

Abstract

Objective

The objective of the study is characterization of novel calcium and zinc-loaded electrospun matrices to be used for periodontal regeneration.

Materials and methods

A polymethylmetacrylate-based membrane was calcium or zinc loaded. Matrices were characterized morphologically by atomic force and scanning electron microscopy and mechanically probed by a nanoindenter. Biomimetic calcium phosphate precipitation on polymeric tissues was assessed. Cell viability tests were performed using oral mucosa fibroblasts. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests or by ANOVA and Student-Newman-Keuls multiple comparisons.

Results

Zinc and calcium loading on matrices did not modify their morphology but increased nanomechanical properties and decreased nanoroughness. Precipitation of calcium and phosphate on the matrix surfaces was observed in zinc-loaded specimens. Matrices were found to be non-toxic to cells in all the assays. Calcium- and zinc-loaded scaffolds presented a very low cytotoxic effect.

Conclusions

Zinc-loaded membranes permit cell viability and promoted mineral precipitation in physiological conditions. Based on the tested nanomechanical properties and scaffold architecture, the proposed membranes may be suitable for cell proliferation.

Clinical relevance

The ability of zinc-loaded matrices to promote precipitation of calcium phosphate deposits, together with their observed non-toxicity and its surface chemistry allowing covalent binding of proteins, may offer new strategies for periodontal regeneration.

http://ift.tt/2liJICP

Platelet biology and the rationale of PRP therapy in chronic wounds

Abstract

For the past four decades, platelets have been thought to function only in hemostatic processes. With reference to recent research, today, it is known that platelets also play important roles in tissue regeneration and immunological processes. The keystone of the use of platelet-rich plasma (PRP) for the treatment of chronic wounds lays in the molecular composition of thrombocytes, which are rich in growth factors and other biologically active substances. PRP forms a matrix for cells and thus promotes wound healing processes. Harvesting PRP is relatively uncomplicated, minimally invasive, and potentially available for each patient. In this review, we provide an overview of the biology of the thrombocyte to better understand the effects of PRP. Additionally, we reviewed published studies, analyzing the effectiveness of PRP for the treatment of chronic wounds.

Level of evidence: Not ratable.

http://ift.tt/2kL0xEB

Visfatin correlates with hot flashes in postmenopausal women with metabolic syndrome: effects of genistein

Abstract

During menopause, an increased prevalence of metabolic syndrome (MetS) and central obesity seems to increase hot flashes (HFs). Visfatin is an inflammatory adipokine secreted by visceral fat. We investigated visfatin levels and its relationship with hot flash number and BMI, in postmenopausal women with MetS. We also evaluated the effect of genistein, an isoflavone effective in reducing HFs, on visfatin levels and HFs after 1 year of treatment. This was a randomized, double-blind, placebo-controlled trial. Postmenopausal women with MetS were randomly assigned to receive placebo (n = 60) or 54 mg genistein (n = 60), daily for 1 year. As main outcome measures, hot flashes number and circulating visfatin levels were evaluated. Visfatin significantly correlated with BMI and HFs number in women with MetS at basal. After 6 and 12 months, our results indicate a strong correlation and a significant effect of genistein in reducing both HFs and visfatin in women with MetS. The present study suggests that visfatin plays a role in the vasomotor symptoms, at least in postmenopausal women with metabolic syndrome. Genistein may reduce HFs decreasing the circulating levels of this inflammatory adipokine.

http://ift.tt/2ma5EiH

Chronic lymphocytic thyroiditis does not influence the risk of recurrence in patients with papillary thyroid carcinoma and excellent response to initial therapy

Abstract

Background

This study evaluated the recurrence in patients with papillary thyroid cancer and an excellent response to initial therapy, comparing those with and without chronic lymphocytic thyroiditis.

Methods

This was a prospective study. Patients who met the following criteria were selected: diagnosis of papillary thyroid cancer; submitted to total thyroidectomy followed or not by ablation with ¹³¹I; and neck ultrasonography without abnormalities, nonstimulated thyroglobulina (Tg) ≤0.2 ng/ml, and undetectable antithyroglobulin antibodies (TgAb) 12–18 months after initial therapy. The patients were divided into two groups: group A, with chronic lymphocytic thyroiditis on histology; group B, without chronic lymphocytic thyroiditis on histology.

Results

Groups A and B were similar in terms of sex and age of the patients, characteristics of the tumor, tumor-node-metastase stage and risk category. The time of follow-up ranged from 24 to 120 months (median 66 months). During follow-up, 5 patients of group A (2.6 %) and 9 patients of group B (2 %) developed recurrence (p = 0.77). Patients with chronic lymphocytic thyroiditis were more likely to progress to persistently borderline TgAb. No patient had positive TgAb (above the reference value) during follow-up. Recurrences occurred in 12/588 patients (2 %) with undetectable TgAb in all measurements, in 1/32 (3.1 %) with detectable TgAb on some occasion but that returned to undetectable spontaneously, and in 1/13 (7.7 %) with persistently borderline TgAb. These rates did not differ significantly (p = 0.25).

Conclusion

The results of the present study showed the absence of an association between chronic lymphocytic thyroiditis and recurrence risk at least in patients with an excellent response to initial therapy.

http://ift.tt/2lwMPJV

Pituitary magnetic resonance imaging in Cushing’s disease

Abstract

Adrenocorticotropin-secreting pituitary tumor represents about 10 % of pituitary adenomas and at the time of diagnosis most of them are microadenomas. Transsphenoidal surgery is the first-line treatment of Cushing's disease and accurate localization of the tumor within the gland is essential for selectively removing the lesion and preserving normal pituitary function. Magnetic resonance imaging is the best imaging modality for the detection of pituitary tumors, but adrenocorticotropin-secreting pituitary microadenomas are not correctly identified in 30–50 % of cases, because of their size, location, and enhancing characteristics. Several recent studies were performed with the purpose of better localizing the adrenocorticotropin-secreting microadenomas through the use in magnetic resonance imaging of specific sequences, reduced contrast medium dose and high-field technology. Therefore, an improved imaging technique for pituitary disease is mandatory in the suspect of Cushing's disease. The aims of this paper are to present an overview of pituitary magnetic resonance imaging in the diagnosis of Cushing's disease and to provide a magnetic resonance imaging protocol to be followed in case of suspicion adrenocorticotropin-secreting pituitary adenoma.

http://ift.tt/2magXXQ

Proopiomelanocortin, glucocorticoid, and CRH receptor expression in human ACTH-secreting pituitary adenomas

Abstract

ACTH-secreting pituitary tumors are by definition partially autonomous, i.e., secrete ACTH independent of physiological control. However, only few, small-sized studies on proopiomelanocortin (POMC) and its regulation by corticotropin-releasing hormone (CRH) or glucocorticoids are available. Objective of the present study was to report on constitutive and CRH- and dexamethasone-regulated POMC, CRH (CRH-R1), and glucocorticoid receptor (NR3C1) gene expression in a large series of human corticotrope adenomas. Fifty-three ACTH-secreting adenomas were incubated with 10 nM CRH or 10 nM dexamethasone for 24 h. POMC, CRH-R1, NR3C1, and its alpha and beta isoforms were quantified and medium ACTH measured. Constitutive POMC expression proved extremely variable, with macroadenomas exhibiting higher levels than microadenomas. POMC increased during CRH in most specimens; conversely, changes induced by dexamethasone were varied, ranging from decrease to paradoxical increase. No correlation between POMC and ACTH was detected in any experimental condition. CRH-R1 expression was not linked to the response to CRH while NR3C1 was expressed at greater levels in specimens who failed to inhibit during dexamethasone; glucocorticoid receptor α was the more abundant isoform and subject to down-regulation by dexamethasone. Our results demonstrate a considerable variability in POMC expression among tumors and no correlation between POMC and ACTH, suggesting that POMC peptide processing/transport plays a major role in modulating ACTH secretion. Further, CRH-R1 and NR3C1 expression were not linked to the expected ligand-induced outcome, indicating that receptor signaling rather than abundance determines corticotrope responses. Our findings pave the way to new avenues of research into Cushing's disease pathophysiology.

http://ift.tt/2lwBDwA

Determinants of Policy Decisions for Non-Commercial Drivers with OSA: An Integrative Review

Excessive daytime sleepiness and reduced cognitive funcitioning secondary to obstructive sleep apnea (OSA) have been identified as an important health-related risk in commercial transportation with, possibly, an increased chance of road accidents. This has resulted in a variety of policies and restrictions imposed on commercial drivers. Here we review current knowledge to assess whether available data are sufficient to guide policy decisions concerning restrictions for non-commercial drivers. The review shows that there is a lack of uniformity among different consensus conferences and guidelines as to how to deal with drivers with OSA.

http://ift.tt/2luWj87

Thanks to Reviewers 2016

http://ift.tt/2lYSR39

A systematic review of known interventions for the treatment of chronic non-hypovolaemic hypotonic hyponatraemia and a meta-analysis of the vaptans

Abstract

International and national guidelines on the treatment of chronic non-hypovolaemic hypotonic hyponatraemia differ; therefore we have undertaken this systematic review and meta-analysis to investigate the efficacy and safety of interventions for the treatment of chronic non-hypovolaemic hypotonic hyponatraemia.

Following registration of the review protocol with PROSPERO, systematic literature searches were conducted to identify randomised and quasi-randomised controlled trials assessing any degree of fluid restriction or any drug treatment with the aim of increasing serum sodium concentration in patients with chronic non-hypovolaemic hypotonic hyponatraemia. Where appropriate, outcome data were synthesised in a meta-analysis.

45,716 bibliographic records were identified from the searches and 18 trials (assessing conivaptan, lixivaptan, tolvaptan and satavaptan) met the eligibility criteria. Results suggest that all four vasopressin receptor agonists ("vaptans"), significantly improve serum sodium concentration. Lixivaptan, satavaptan and tolvaptan were associated with greater rates of response versus placebo. There was no evidence of a difference between each of the vaptans compared with placebo for mortality, discontinuation and rates of hypernatraemia. No RCT evidence of treatments other than the vaptans for hyponatraemia such as oral urea, salt tablets, mannitol, loop diuretics demeclocycline or lithium was identified.

Vaptans demonstrated superiority over placebo for outcomes relating to serum sodium correction. Few trials documented the potential benefit of vaptans on change in health-related quality of life as a result of treatment. There was also a lack of high-quality RCT evidence on the comparative efficacy of the vaptans and other treatment strategies for the treatment of chronic non-hypovolaemic hypotonic hyponatraemia.

This article is protected by copyright. All rights reserved.

http://ift.tt/2lwh8QU

CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin

Publication date: Available online 14 February 2017
Source:Immunity
Author(s): Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, Elisa Martini, Samuel C. Chiang, Nicole Marquardt, Anna Gibbs, Ebba Detlofsson, Andrea Introini, Marianne Forkel, Charlotte Höög, Annelie Tjernlund, Jakob Michaëlsson, Lasse Folkersen, Jenny Mjösberg, Lennart Blomqvist, Marcus Ehrström, Mona Ståhle, Yenan T. Bryceson, Liv Eidsmo
Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8⁺ Trm cells on a compartmental and functional basis. In human skin epithelia, CD8⁺CD49a⁺ Trm cells produced interferon-γ, whereas CD8⁺CD49a⁻ Trm cells produced interleukin-17 (IL-17). In addition, CD8⁺CD49a⁺ Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response. In skin from patients with vitiligo, where melanocytes are eradicated locally, CD8⁺CD49a⁺ Trm cells that constitutively expressed perforin and granzyme B accumulated both in the epidermis and dermis. Conversely, CD8⁺CD49a^– Trm cells from psoriasis lesions predominantly generated IL-17 responses that promote local inflammation in this skin disease. Overall, CD49a expression delineates CD8⁺ Trm cell specialization in human epithelial barriers and correlates with the effector cell balance found in distinct inflammatory skin diseases.

Graphical abstract

Teaser

Tissue-resident memory T (Trm) cells provide localized adaptive immunity in peripheral tissues. Cheuk et al. identify cytotoxic CD49a⁺CD8⁺ Trm cells and IL-17-producing CD49a⁻CD8⁺ Trm cells in healthy human skin. The functional dichotomy of pathogenic Trm cells based on CD49a expression is preserved in focal skin diseases vitiligo and psoriasis.


http://ift.tt/2kK5xt2

A Relay Pathway between Arginine and Tryptophan Metabolism Confers Immunosuppressive Properties on Dendritic Cells

Publication date: Available online 14 February 2017
Source:Immunity
Author(s): Giada Mondanelli, Roberta Bianchi, Maria Teresa Pallotta, Ciriana Orabona, Elisa Albini, Alberta Iacono, Maria Laura Belladonna, Carmine Vacca, Francesca Fallarino, Antonio Macchiarulo, Stefano Ugel, Vincenzo Bronte, Federica Gevi, Lello Zolla, Auke Verhaar, Maikel Peppelenbosch, Emilia Maria Cristina Mazza, Silvio Bicciato, Yasmina Laouar, Laura Santambrogio, Paolo Puccetti, Claudia Volpi, Ursula Grohmann
Arginase 1 (Arg1) and indoleamine 2,3-dioxygenase 1 (IDO1) are immunoregulatory enzymes catalyzing the degradation of l-arginine and l-tryptophan, respectively, resulting in local amino acid deprivation. In addition, unlike Arg1, IDO1 is also endowed with non-enzymatic signaling activity in dendritic cells (DCs). Despite considerable knowledge of their individual biology, no integrated functions of Arg1 and IDO1 have been reported yet. We found that IDO1 phosphorylation and consequent activation of IDO1 signaling in DCs was strictly dependent on prior expression of Arg1 and Arg1-dependent production of polyamines. Polyamines, either produced by DCs or released by bystander Arg1⁺ myeloid-derived suppressor cells, conditioned DCs toward an IDO1-dependent, immunosuppressive phenotype via activation of the Src kinase, which has IDO1-phosphorylating activity. Thus our data indicate that Arg1 and IDO1 are linked by an entwined pathway in immunometabolism and that their joint modulation could represent an important target for effective immunotherapy in several disease settings.

Teaser

Arginase 1 (Arg1) and indoleamine 2,3-dioxygenase 1 (IDO1) are immunosuppressive enzymes known to operate in distinct immune cells. Mondanelli and colleagues demonstrate that Arg1 and IDO1 cooperate in conferring long-term, immunosuppressive effects to dendritic cells.


http://ift.tt/2kKeSRE