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PMID: 24613091 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Immunity ·Vol. 40 ·No. 3 ·2014-03-20 ·Pages 425-35

Halim TY, Steer CA, Mathä L, Gold MJ, Martinez-Gonzalez I, McNagny KM, McKenzie AN, Takei F

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.

MeSH Terms
Adaptive Immunity Allergens/administration & dosage,immunology Animals CD40 Antigens/metabolism Cell Differentiation/drug effects Cell Movement/drug effects,immunology Dendritic Cells/immunology,metabolism Disease Models, Animal Hypersensitivity/genetics,immunology Immunity, Innate Interleukin-13/metabolism,pharmacology Interleukin-4/immunology,metabolism Lymph Nodes/immunology Mice Mice, Knockout Papain/immunology Pneumonia/genetics,immunology T-Lymphocytes, Helper-Inducer/immunology Th2 Cells/cytology,drug effects,immunology
Chemicals
Allergens CD40 Antigens Interleukin-13 Interleukin-4 Papain
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Halim Timotheus Y F
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.
Steer Catherine A
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.
Mathä Laura
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.
Gold Matthew J
Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Martinez-Gonzalez Itziar
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.
McNagny Kelly M
Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
McKenzie Andrew N J
Medical Research Council, Laboratory of Molecular Biology, Cambridge, Cambridgeshire CB2 0QH, UK.
Takei Fumio
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.
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2014.01.011
Email
ftakei@bccrc.ca
Published
2014-03-20
Epub
2014-00-06
Pages
425-35
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC4210641
Subset
IM
Grants
Medical Research Council · MC_U105178805 · United Kingdom
CIHR · Canada
Corrections
CommentIn
PMID: 24656044
CommentIn
PMID: 24722478
External Links
PubMed source DOI: 10.1016/j.immuni.2014.01.011 PMC Full Text View journal details
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