IL-33 controls gd T cell-mediated resistance to skin-penetrating helminths

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B694
Abstract ID: 5375

Presenting Author:
E. Evonne Jean , Graduate Student Researcher at Univ. of Pennsylvania Perelman Sch. of Med.

Abstract:

Interleukin 33 (IL-33) is an alarmin cytokine thought to be released from damaged epithelia that is essential for protection against gastrointestinal (GI) helminth (worm) infection, but whether IL-33 drives protective immunity in cutaneous helminth infection remains unclear. Herein, we developed a percutaneous infection model using the GI nematode Strongylodies ratti to better understand the role for IL-33 in cutaneous immunity against larval stages.  Data show that C57BL/6 mice develop resistance to percutaneous infection upon secondary challenge in an IL-33 dependent manner. Mechanistically, we find that loss of IL-33 impairs recruitment of gd (gamma delta) T cells but not CD4+ T cells that express the IL-33 receptor ST2 in the skin. Furthermore, gene deficient mice that lack all gd T cells show impaired immunity against S. ratti indicating an essential role for this lymphocyte population in IL-33 dependent acquired resistance. Unexpectedly, mice lacking the Type 2 transcription factor STAT6 (Signal transducer and activator of transcription 6), have no defects in primary or secondary cutaneous immunity, indicating that IL-33 drives a non-canonical Type 2 host protective response. Our work implies that IL-33 that drives acquired immunity against helminths, potentially through regulating gd T cell effector function(s). Ongoing studies seek to understand how gd T cells change theintergrity of the cutaneous epithelial barrier in an IL-33 dependent manner.