Marginating transitional B cells modulate neutrophils in the lung during inflammation and pneumonia.

Autor:	Podstawka J; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Department of Critical Care, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Sinha S; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada., Hiroki CH; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Department of Critical Care, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Sarden N; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Department of Critical Care, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Granton E; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Department of Critical Care, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Labit E; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada., Kim JH; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Department of Critical Care, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Andonegui G; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Department of Critical Care, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Lou Y; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Department of Critical Care, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Snarr BD; Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada., Sheppard DC; Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.; Division of Infectious Diseases, McGill University Health Centre, Montreal, Quebec, Canada.; Department of Medical Microbiology, McGill University Health Centre, Montreal, Quebec, Canada., Rosin NL; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada., Biernaskie J; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.; Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Yipp BG; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Department of Critical Care, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2021 Sep 06; Vol. 218 (9). Date of Electronic Publication: 2021 Jul 27.
DOI:	10.1084/jem.20210409
Abstrakt:	Pulmonary innate immunity is required for host defense; however, excessive neutrophil inflammation can cause life-threatening acute lung injury. B lymphocytes can be regulatory, yet little is known about peripheral transitional IgM+ B cells in terms of regulatory properties. Using single-cell RNA sequencing, we discovered eight IgM+ B cell subsets with unique gene regulatory networks in the lung circulation dominated by transitional type 1 B and type 2 B (T2B) cells. Lung intravital confocal microscopy revealed that T2B cells marginate in the pulmonary capillaries via CD49e and require CXCL13 and CXCR5. During lung inflammation, marginated T2B cells dampened excessive neutrophil vascular inflammation via the specialized proresolving molecule lipoxin A4 (LXA4). Exogenous CXCL13 dampened excessive neutrophilic inflammation by increasing marginated B cells, and LXA4 recapitulated neutrophil regulation in B cell-deficient mice during inflammation and fungal pneumonia. Thus, the lung microvasculature is enriched in multiple IgM+ B cell subsets with marginating capillary T2B cells that dampen neutrophil responses. Competing Interests: Disclosures: The authors declare no competing interests exist. (© 2021 Podstawka et al.)
Databáze:	MEDLINE
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