Gene expression profile from mouse natural helper cell

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 cytokines1,2. We report here 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 express c-Kit, Sca-1, IL-7R and IL-33R. Similar lymphoid clusters were found in both human and mouse mesentery and we term this tissue FALC for fat-associated lymphoid cluster. FALC Lin-c-Kit+Sca-1+ cells are distinct from lymphoid progenitors3 and lymphoid tissue inducer (LTi) cells4. These cells proliferate in response to IL-2 and produce large amounts of Th2 cytokines such as IL-5, IL-6 and IL-13. IL-5 and IL-6 regulate B cell antibody production and self-renewal of B1 cells5-7. Indeed, FALC Lin-c-Kit+Sca-1+ cells support the self-renewal of B1 cells and enhance IgA production. IL-5 and IL-13 mediate allergic inflammation and protection against helminth infection8,9. Upon helminth infection and in response to IL-33, FALC Lin-c-Kit+Sca-1+ cells produce large amounts of IL-13, 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 Th2-type innate lymphocytes and we propose that these cells be called natural helper cells.

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Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, Furusawa J, Ohtani M, Fujii H, Koyasu S