title: Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells.
abstract: Innate immune responses are important in combating various microbes during the early phases of infection. Natural killer (NK) cells are innate lymphocytes that, unlike T and B lymphocytes, do not express antigen receptors but rapidly exhibit cytotoxic activities against virus-infected cells and produce various cytokines. Here we report a new type of innate lymphocyte present in a novel lymphoid structure associated with adipose tissues in the peritoneal cavity. These cells do not express lineage (Lin) markers but do express c-Kit, Sca-1 (also known as Ly6a), IL7R and IL33R. Similar lymphoid clusters were found in both human and mouse mesentery and we term this tissue 'FALC' (fat-associated lymphoid cluster). FALC Lin(-)c-Kit(+)Sca-1(+) cells are distinct from lymphoid progenitors and lymphoid tissue inducer cells. These cells proliferate in response to IL2 and produce large amounts of T(H)2 cytokines such as IL5, IL6 and IL13. IL5 and IL6 regulate B-cell antibody production and self-renewal of B1 cells. Indeed, FALC Lin(-)c-Kit(+)Sca-1(+) cells support the self-renewal of B1 cells and enhance IgA production. IL5 and IL13 mediate allergic inflammation and protection against helminth infection. After helminth infection and in response to IL33, FALC Lin(-)c-Kit(+)Sca-1(+) cells produce large amounts of IL13, which leads to goblet cell hyperplasia-a critical step for helminth expulsion. In mice devoid of FALC Lin(-)c-Kit(+)Sca-1(+) cells, such goblet cell hyperplasia was not induced. Thus, FALC Lin(-)c-Kit(+)Sca-1(+) cells are T(H)2-type innate lymphocytes, and we propose that these cells be called 'natural helper cells'.
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Moro
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
authors.forename: Masanobu
authors.initials: M
authors.lastname: Tanabe
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Tomokatsu
authors.initials: T
authors.lastname: Ikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawamoto
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Furusawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Ohtani
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koyasu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000276:immunology*; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D008214:Lymphocytes / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D008643:Mesentery / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009348:Nematoda / Q000502:physiology; D009349:Nematode Infections / Q000276:immunology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000950:Antigens, Ly; D016207:Cytokines; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit