Marginal zone B cells exacerbate endotoxic shock via interleukin-6 secretion induced by Fcα/μR-coupled TLR4 signalling.

Autor: Honda S; Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan., Sato K; Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan., Totsuka N; Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan., Fujiyama S; Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan., Fujimoto M; Department of Dermatology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan., Miyake K; Division of Innate Immunity, Institute of Medical Sciences, University of Tokyo, Shirokanedai, Minatoloku, Tokyo 108-8639, Japan., Nakahashi-Oda C; Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan., Tahara-Hanaoka S; Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan.; Life Science Center of Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan., Shibuya K; Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan., Shibuya A; Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan.; Life Science Center of Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2016 May 05; Vol. 7, pp. 11498. Date of Electronic Publication: 2016 May 05.
DOI: 10.1038/ncomms11498
Abstrakt: Marginal zone (MZ) B cells produce a first wave of antibodies for protection from blood-borne pathogens. However, the role of MZ B cells in inflammatory responses has not been elucidated. Here we show that MZ B cells produce pro-inflammatory cytokines, such as interleukin-6 (IL-6), and exacerbate systemic inflammatory responses to lipopolysaccharide (LPS). After intravenous injection of LPS or E. coli, mice deficient in MZ B cells or IL-6 only in MZ B cells have attenuated systemic inflammatory responses and prolonged survival compared with wild-type mice. LPS directly stimulates MZ B cells via Toll-like receptor 4 (TLR4) and MyD88 pathways for IL-6 production. Furthermore, TLR4 requires physical and functional association with Fcα/μR (CD351) for its oligomer formation, NF-κB signalling and IL-6 production from MZ B cells; this association is responsible for systemic inflammatory responses and endotoxic shock. These results reveal a pro-inflammatory role of MZ B cells in endotoxic shock.
Databáze: MEDLINE
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