title: Identification of a novel type 2 innate immunocyte with the ability to enhance IgE production.
abstract: Fas (CD95), a member of the tumor necrosis factor receptor superfamily, mediates apoptosis-inducing signals in its expressing cells, especially in self-reactive cells. We recently reported that Fas(-/-) mice with a BALB/c background (BALB/c Fas(-/-) mice) developed blepharitis with allergic inflammation that was accompanied by hyper-IgE production. Here, we found a novel type of immunocyte in the spleen of BALB/c Fas(-/-) mice, which enhanced the production of IgE by B cells in the presence of IL-4 and CD40 signaling in vitro. The immunocyte did not express lineage markers but expressed Thy-1 and Sca-1 just like recently identified type 2 innate lymphoid cells, such as natural helper (NH) cells and nuocytes. However, they did not express c-Kit, IL-7R and IL-33R (T1/ST2), important markers of type 2 innate lymphoid cells. Instead, our identified Lin(-)Thy-1(+)Sca-1(+) cells expressed IL-18R and secreted Th2 cytokines when co-cultured with B cells or when stimulated with IL-18 and IL-2. Moreover, we found essentially the same type of cells in BALB/c wild-type mice as in BALB/c Fas(-/-) mice, which enhanced IgE production in contact with B cells in vitro. These cells from BALB/c wild-type mice expressed Fas and were sensitive to Fas-mediated apoptosis. Collectively, the newly identified Lin(-)Thy-1(+)Sca-1(+) cell, which we designated a F-NH cell (Fas-expressing natural helper cell), is a novel type 2 innate immunocyte with activity to enhance IgE production from B cells with the help of IL-4 and CD40 signaling. F-NH cells may play an important role in the development of chronic allergic inflammation.
authors: Laboratory of Molecular and Cellular Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
authors: Ayumi
authors: A
authors: Fukuoka
authors: Shizue
authors: S
authors: Futatsugi-Yumikura
authors: Suzuka
authors: S
authors: Takahashi
authors: Hirotaka
authors: H
authors: Kazama
authors: Tomonori
authors: T
authors: Iyoda
authors: Tomohiro
authors: T
authors: Yoshimoto
authors: Kayo
authors: K
authors: Inaba
authors: Kenji
authors: K
authors: Nakanishi
authors: Shin
authors: S
authors: Yonehara
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007113:Immunity, Innate / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019014:fas Receptor / Q000172:deficiency / Q000378:metabolism
chemical_list: C491899:Fas protein, mouse; D019014:fas Receptor; D007073:Immunoglobulin E
keywords: Fas; IL-18; IgE; allergy; innate immunocyte