Epidermal Growth Factor Receptor Expression Licenses Type-2 Helper T Cells to Function in a T Cell Receptor-Independent Fashion

Publication date: 17 October 2017
Source:Immunity, Volume 47, Issue 4
Author(s): Carlos M. Minutti, Sebastian Drube, Natalie Blair, Christian Schwartz, Jame C. McCrae, Andrew N. McKenzie, Thomas Kamradt, Michal Mokry, Paul J. Coffer, Maria Sibilia, Alice J. Sijts, Padraic G. Fallon, Rick M. Maizels, Dietmar M. Zaiss
Gastro-intestinal helminth infections trigger the release of interleukin-33 (IL-33), which induces type-2 helper T cells (Th2 cells) at the site of infection to produce IL-13, thereby contributing to host resistance in a T cell receptor (TCR)-independent manner. Here, we show that, as a prerequisite for IL-33-induced IL-13 secretion, Th2 cells required the expression of the epidermal growth factor receptor (EGFR) and of its ligand, amphiregulin, for the formation of a signaling complex between T1/ST2 (the IL-33R) and EGFR. This shared signaling complex allowed IL-33 to induce the EGFR-mediated activation of the MAP-kinase signaling pathway and consequently the expression of IL-13. Lack of EGFR expression on T cells abrogated IL-13 expression in infected tissues and impaired host resistance. EGFR expression on Th2 cells was TCR-signaling dependent, and therefore, our data reveal a mechanism by which antigen presentation controls the innate effector function of Th2 cells at the site of inflammation.

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Teaser

At the site of infection, Th2 cells secrete IL-13 upon exposure to IL-33. Minutti et al. now show that TCR-induced expression of the EGFR and its ligand amphiregulin was essential for IL-33-induced IL-13 secretion, revealing a mechanism whereby antigen-specific activation controls the innate effector function of Th2 cells.


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