Dysfunction of regulatory T cells in patients with ankylosing spondylitis is associated with a loss of Tim-3

Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Mingfei Wang, Chengyi Liu, Allen Bond, Jun Yang, Xu Zhou, Jian Wang, Bin Ji
An expansion of regulatory T cells (Tregs) in ankylosing spondylitis (AS) was observed. However, AS patients continue to exhibit aberrant inflammation. In this study, we collected PBMCs from 26 AS patients and 26 healthy controls, and investigated the functional capacity of Treg cells from these subjects. In AS patients, the frequency of CD4⁺CD25⁺Foxp3⁺CD127⁻ Treg cells was slightly increased compared to healthy controls, but the level of Foxp3 MFI in AS patient CD4⁺CD25⁺Foxp3⁺CD127⁻ Treg cells was significantly lower than that in healthy control CD4⁺CD25⁺Foxp3⁺CD127⁻ Treg cells. Tim-3⁺ Treg cells were previously shown to present stronger suppressive capacity than Tim-3⁻ Treg cells. Here, we discovered that the Tim-3⁺ cell frequency in CD4⁺CD25⁺Foxp3⁺CD127⁻ Treg cells was significantly lower in AS patients. In both healthy volunteers and AS patients, Tim-3⁺ Treg cells demonstrated higher transcription of Foxp3, IL-10 and TGF-β, higher secretion of IL-10 and TGF-β, and stronger inhibition of conventional T cell inflammation, than Tim-3⁻ Treg cells. In some but not all functional aspects, the Tim-3⁺ Treg cells from healthy controls were more potent than the Tim-3⁺ Treg cells from AS patients. Collectively, these results demonstrated two Treg-related impairments in AS patients. First, the frequency of the more potent Tim-3⁺ Treg cells was lower in AS patients, and second, some of Tim-3⁺ Treg-mediated functions were less potent in AS patients. Interestingly, the ratio of Tim-3⁻/Tim-3⁺ Treg cells in AS patients was directly correlated with the Bath ankylosing spondylitis disease activity index (BASDAI) score, the C-reactive protein (CRP) level, and the erythrocyte sedimentation rate (ESR). Given the fact that Tim-3⁺ Treg cells presented potent suppressive functions, Tim-3⁺ Treg cells and Tim-3⁺ Treg-mediated mechanisms might be potential candidates for immunotherapies in AS patients.



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