CD153/CD30 signaling promotes age-dependent tertiary lymphoid tissue expansion and kidney injury.

Autor:	Sato Y; Department of Nephrology.; Medical Innovation Center TMK Project, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Oguchi A; Department of Nephrology.; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan., Fukushima Y; Department of Immunosenescence and.; Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Masuda K; Department of Immunology, Institute for Frontier Medical Science, and., Toriu N; Department of Nephrology., Taniguchi K; Department of Nephrology., Yoshikawa T; Department of Nephrology., Cui X; Department of Nephrology.; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan., Kondo M; Department of Nephrology., Hosoi T; Medical Innovation Center TMK Project, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Komidori S; Department of Nephrology., Shimizu Y; Department of Nephrology., Fujita H; Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Jiang L; Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan., Kong Y; Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan., Yamanashi T; Medical Sciences Innovation Hub Program, RIKEN, Tokyo, Japan., Seita J; Medical Sciences Innovation Hub Program, RIKEN, Tokyo, Japan., Yamamoto T; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan.; Department of Life Science Frontiers, Kyoto University, Kyoto, Japan.; Medical-risk Avoidance Based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Kyoto, Japan., Toyokuni S; Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.; Sydney Medical School, The University of Sydney, New South Wales, Australia., Hamazaki Y; Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.; Laboratory of Immunobiology, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan., Hattori M; Department of Immunosenescence and.; Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Yoshikai Y; Division of Host Defense, Network Center for Infectious Disease, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan., Boor P; Institute of Pathology and.; Department of Nephrology, RWTH University of Aachen, Aachen, Germany., Floege J; Department of Nephrology, RWTH University of Aachen, Aachen, Germany., Kawamoto H; Department of Immunology, Institute for Frontier Medical Science, and., Murakawa Y; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan., Minato N; Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.; DSK Project, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Yanagita M; Department of Nephrology.; Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan.
Jazyk:	angličtina
Zdroj:	The Journal of clinical investigation [J Clin Invest] 2022 Jan 18; Vol. 132 (2).
DOI:	10.1172/JCI146071
Abstrakt:	Tertiary lymphoid tissues (TLTs) facilitate local T and B cell interactions in chronically inflamed organs. However, the cells and molecular pathways that govern TLT formation are poorly defined. Here, we identified TNF superfamily CD153/CD30 signaling between 2 unique age-dependent lymphocyte subpopulations, CD153+PD-1+CD4+ senescence-associated T (SAT) cells and CD30+T-bet+ age-associated B cells (ABCs), as a driver for TLT expansion. SAT cells, which produced ABC-inducing factors IL-21 and IFN-γ, and ABCs progressively accumulated within TLTs in aged kidneys after injury. Notably, in kidney injury models, CD153 or CD30 deficiency impaired functional SAT cell induction, which resulted in reduced ABC numbers and attenuated TLT formation with improved inflammation, fibrosis, and renal function. Attenuated TLT formation after transplantation of CD153-deficient bone marrow further supported the importance of CD153 in immune cells. Clonal analysis revealed that SAT cells and ABCs in the kidneys arose from both local differentiation and recruitment from the spleen. In the synovium of aged rheumatoid arthritis patients, T peripheral helper/T follicular helper cells and ABCs also expressed CD153 and CD30, respectively. Together, our data reveal a previously unappreciated function of CD153/CD30 signaling in TLT formation and propose targeting the CD153/CD30 signaling pathway as a therapeutic target for slowing kidney disease progression.
Databáze:	MEDLINE
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