Naïve T cells sense the cysteine protease allergen papain through the protease activated receptor 2 (PAR2) and propel TH2 immunity

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NIAID	IMMUNO-6

Authors

• T. Barker
• G. Liang
• Z. Xie
• N. Charles
• J. Rivera
• K.M. Druey

Abstract

The initiation of TH2 immunity is not completely understood. We examined early cytokine production, cellular trafficking and signal transduction during TH2 dependent allergic inflammation in mice injected subcutaneously with the protease allergen papain. Transcriptional profiling of the draining lymph nodes (LNs) of papain treated mice revealed an upregulation of Ccl17 and Ccl22, leading to the recruitment of CCR4+ basophils to the LNs. We determined that CD4+ T cells were the principal source of these chemokines and that neither chemokine production nor basophil recruitment were altered in the absence of CD11c+ dendritic cells. Furthermore, papain was recognized by basophils and a subpopulation of naïve CD4+ T cells through the protease activating receptor 2 (PAR2). In the absence of PAR2, CCL17/CCL22 production, basophil recruitment and IL-4 production in response to papain injection were greatly impaired. We propose that following exposure to papain, a subpopulation of naïve T cells provide an initial antigen-unrestricted burst of chemokines, which recruits CCR4+ basophils to the inflamed site. The subsequent production of IL-4 by both these cell types initiates an Ag-specific TH2 response. As such, PAR2 antagonism may be valuable for the treatment of allergic disease.

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