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Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell mediated allergic lung inflammation

Posted March 21, 2014 | Publications

Halim TYF,  Steer CA,  Matha L,  Gold MJ,  Martinez-Gonzalez I,  McNagny KM,  McKenzie ANJ,  Takei F.  Immunity 40:425-435, 2014.

 

Abstract

Naïve  CD4+ T cell differentiation into distinct subsets of T helper (Th) cells is a pivotal process in the initiation of the adaptive immune response.  Allergens predominantly stimulate Th2 cells,  causing allergic inflammation.  However,  why allergens induce Th2 cell differentiation is not well understood.  Here we show that Group 2 Innate Lymphoid Cells (ILC2s) are required to mount a robust Th2 cell response to the protease-allergen papain.  Intranasal administration of papain stimulated ILC2s and Th2 cells, causing allergic lung inflammation and elevated IgE titres.  This process was severely impaired in ILC2-deficient mice.  Whereas IL-4 was dispensable for papain-induced Th2 cell differentiation, ILC2-derived IL-13 was critical as it promoted migration of activated lung dendritic cells into the draining lymph node where they primed naïve T cells to differentiate into Th2 cells.  Papain-induced ILC2 activation and Th2 cell differentiation was IL-33-dependent, suggesting a common pathway in the initiation of Th2 cell responses to allergen.