Epidermal growth factor receptor expression licenses type-2 helper T cells to function in a T cell receptor-independent fashion

Minutti, C. M. et al. (2017) Epidermal growth factor receptor expression licenses type-2 helper T cells to function in a T cell receptor-independent fashion. Immunity, 47(4), 710-722.e6. (doi: 10.1016/j.immuni.2017.09.013) (PMID:29045902) (PMCID:PMC5654729)

Abstract

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.

• Item Type: Articles
• Additional Information: Work in the D.M.Z. laboratory is supported by the Medical Research Council, grant MR/M011755/1, and the European Union, grant CIG-631413 (‘‘EGF-R for Immunity’’). The M.S. laboratory is supported by the Austrian Science Fund (FWF) grants SFB F3518-B20, W1212, and P25925. A.N.M. is funded by the MRC grant U105178805.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Maizels, Professor Rick
• Authors: Minutti, C. M., Drube, S., Blair, N., Schwartz, C., McCrae, J. C., McKenzie, A. N., Kamradt, T., Mokry, M., Coffer, P. J., Sibilia, M., Sijts, A. J., Fallon, P. G., Maizels, R. M., and Zaiss, D. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Immunity
• Publisher: Elsevier
• ISSN: 1074-7613
• ISSN (Online): 1097-4180
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Immunity 47(4):710-722.e6
• Publisher Policy: Reproduced under a Creative Commons license