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Immunity. 2014 Mar 20;40(3):425-35. doi: 10.1016/j.immuni.2014.01.011. Epub 2014 Mar 6.

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

Author information

1
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada; Genetics Graduate Program, College for Interdisciplinary Studies, University of British Columbia, Vancouver, British Columbia V6T 1Z2, Canada; Medical Research Council, Laboratory of Molecular Biology, Cambridge, Cambridgeshire CB2 0QH, UK.
2
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.
3
Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
4
Medical Research Council, Laboratory of Molecular Biology, Cambridge, Cambridgeshire CB2 0QH, UK.
5
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada. Electronic address: ftakei@bccrc.ca.

Abstract

Naive 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 immunoglobulin E titers. This process was severely impaired in ILC2-deficient mice. Whereas interleukin-4 (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 naive 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.

PMID:
24613091
PMCID:
PMC4210641
DOI:
10.1016/j.immuni.2014.01.011
[Indexed for MEDLINE]
Free PMC Article

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