title: Neutrophils license iNKT cells to regulate self-reactive mouse B cell responses.
abstract: The innate responsiveness of the immune system is important not only for quick responses to pathogens but also for the initiation and shaping of the subsequent adaptive immune response. Activation via the cytokine IL-18, a product of inflammasomes, gives rise to a rapid response that includes the production of self-reactive antibodies. As increased concentrations of this cytokine are found in inflammatory diseases, we investigated the origin of the B cell response and its regulation. We identified an accumulation of B cell-helper neutrophils in the spleen that interacted with innate-type invariant natural killer T cells (iNKT cells) to regulate B cell responses. We found that neutrophil-dependent expression of the death-receptor ligand FasL by iNKT cells was needed to restrict autoantibody production. Neutrophils can thus license iNKT cells to regulate potentially harmful autoreactive B cell responses during inflammasome-driven inflammation.
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.
authors: Thomas
authors: T
authors: Hägglöf
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.
authors: Saikiran K
authors: SK
authors: Sedimbi
authors: Trudeau Institute, Saranac Lake, New York, USA.
authors: Jennifer L
authors: http://orcid.org/0000-0001-8841-9401
authors: JL
authors: Yates
authors: Department of Clinical Neuroscience, Karolinska Institutet, Centre for Molecular Medicine, Karolinska University Hospital at Solna, Solna, Sweden.
authors: Roham
authors: http://orcid.org/0000-0002-0864-6098
authors: R
authors: Parsa
authors: Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors: Briana Hauff
authors: BH
authors: Salas
authors: Department of Clinical Neuroscience, Karolinska Institutet, Centre for Molecular Medicine, Karolinska University Hospital at Solna, Solna, Sweden.
authors: Robert A
authors: RA
authors: Harris
authors: Trudeau Institute, Saranac Lake, New York, USA.|Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors: Elizabeth A
authors: EA
authors: Leadbetter
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.
authors: Mikael C I
authors: http://orcid.org/0000-0001-5582-614X
authors: MC
authors: Karlsson
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D007113:Immunity, Innate; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000276:immunology*; D020382:Interleukin-18 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D053222:Fas Ligand Protein; D058847:Inflammasomes; D020382:Interleukin-18