title: Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation.
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.
authors.affiliation: 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.
authors.forename: Timotheus Y F
authors.initials: TY
authors.lastname: Halim
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Steer
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Mathä
authors.affiliation: Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gold
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Itziar
authors.initials: I
authors.lastname: Martinez-Gonzalez
authors.affiliation: Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McNagny
authors.affiliation: Medical Research Council, Laboratory of Molecular Biology, Cambridge, Cambridgeshire CB2 0QH, UK.
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: McKenzie
authors.affiliation: 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.
authors.forename: Fumio
authors.initials: F
authors.lastname: Takei
mesh_terms: D056704:Adaptive Immunity; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D019013:CD40 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate; D018793:Interleukin-13 / Q000378:metabolism / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010206:Papain / Q000276:immunology; D011014:Pneumonia / Q000235:genetics / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D000485:Allergens; D019013:CD40 Antigens; D018793:Interleukin-13; D015847:Interleukin-4; D010206:Papain