3 years ago

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

Epidermal Growth Factor Receptor Expression Licenses Type-2 Helper T Cells to Function in a T Cell Receptor-Independent Fashion
Sebastian Drube, Rick M. Maizels, Padraic G. Fallon, Natalie Blair, Paul J. Coffer, Carlos M. Minutti, Maria Sibilia, Christian Schwartz, Michal Mokry, Dietmar M. Zaiss, Thomas Kamradt, Andrew N. McKenzie, Alice J. Sijts, Jame C. McCrae

Summary

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.

Publisher URL: http://www.cell.com/immunity/fulltext/S1074-7613(17)30424-7

DOI: 10.1016/j.immuni.2017.09.013

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