title: Retinoic-acid-receptor-related orphan nuclear receptor alpha is required for natural helper cell development and allergic inflammation.
abstract: Natural helper (NH) cells are innate lymphoid cells (ILCs) that produce T helper-2 (Th2)-cell-type cytokines in the lung- and gut-associated lymphoid tissues. Currently, the lineage relationship between NH cells in different tissues and between NH cells and interleukin-22 (IL-22)-producing retinoic-acid-receptor-related orphan receptor (ROR)γt-positive ILCs is unclear. Here, we report that NH cells express RORα, but not RORγt. RORα-deficient, but not RORγt-deficient, mice lacked NH cells in all tissues, whereas all other lymphocytes, including RORγt(+) ILCs, were unaffected. NH-cell-deficient mice generated by RORα-deficient bone-marrow transplantation had normal Th2 cell responses but failed to develop acute lung inflammation in response to protease allergen, thus confirming the essential role of NH cells in allergic lung inflammation. We have also identified RORα-dependent NH cell progenitors in the bone marrow. Thus, all NH cells belong to a unique RORα-dependent cell lineage separate from other lymphoid cell lineages.
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Timotheus Y F
authors.initials: TY
authors.lastname: Halim
authors.forename: Aric
authors.initials: A
authors.lastname: MacLaren
authors.forename: Mark T
authors.initials: MT
authors.lastname: Romanish
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gold
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McNagny
authors.forename: Fumio
authors.initials: F
authors.lastname: Takei
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D019070:Cell Lineage / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics / Q000276:immunology*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000276:immunology; D010206:Papain / Q000276:immunology; D011014:Pneumonia / Q000235:genetics / Q000276:immunology*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D000950:Antigens, Ly; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539739:Rora protein, mouse; D019009:Proto-Oncogene Proteins c-kit; D010206:Papain