Innate production of TH 2 cytokines by adipose tissue-associated c-Kit+ Sca-1+ lymphoid cells

Kazuyo Moro, Taketo Yamada, Masanobu Tanabe, Tsutomu Takeuchi, Tomokatsu Ikawa, Hiroshi Kawamoto, Jun Ichi Furusawa, Masashi Ohtani, Hideki Fujii, Shigeo Koyasu

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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'.

Original languageEnglish
Pages (from-to)540-544
Number of pages5
JournalNature
Volume463
Issue number7280
DOIs
Publication statusPublished - 2010 Jan 28

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Moro, K., Yamada, T., Tanabe, M., Takeuchi, T., Ikawa, T., Kawamoto, H., Furusawa, J. I., Ohtani, M., Fujii, H., & Koyasu, S. (2010). Innate production of TH 2 cytokines by adipose tissue-associated c-Kit+ Sca-1+ lymphoid cells. Nature, 463(7280), 540-544. https://doi.org/10.1038/nature08636