1. Podocyte SIRPα reduction aggravates lupus nephritis via promoting T cell inflammatory responses.
- Author
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Qian B, Lu R, Mao S, Chen Y, Yang M, Zhang W, Zhang M, Zhu D, Liu Z, Zen K, and Li L
- Subjects
- Animals, Mice, Mice, Inbred C57BL, Inflammation pathology, Inflammation metabolism, Phosphorylation, Lymphocyte Activation immunology, Humans, Antigen Presentation immunology, Female, Podocytes metabolism, Podocytes pathology, Podocytes immunology, Lupus Nephritis pathology, Lupus Nephritis immunology, Lupus Nephritis metabolism, Receptors, Immunologic metabolism, Receptors, Immunologic genetics, T-Lymphocytes immunology, T-Lymphocytes metabolism, Syk Kinase metabolism
- Abstract
Signal-regulatory protein alpha (SIRPα) has recently been found to be highly expressed in podocytes and is essential for maintaining podocyte function. However, its immunoregulatory function in podocytes remains elusive. Here, we report that SIRPα controls podocyte antigen presentation in specific T cell activation via inhibiting spleen tyrosine kinase (Syk) phosphorylation. First, podocyte SIRPα under lupus nephritis (LN) conditions is strongly downregulated. Second, podocyte-specific deletion of SIRPα exacerbates renal disease progression in lupus-prone mice, as evidenced by an increase in T cell infiltration. Third, SIRPα deletion or knockdown enhances podocyte antigen presentation, which activates specific T cells, via enhancing Syk phosphorylation. Supporting this, Syk inhibitor GS-9973 prevents podocyte antigen presentation, resulting in a decrease of T cell activation and mitigation of renal disease caused by SIRPα knockdown or deletion. Our findings reveal an immunoregulatory role of SIRPα loss in promoting podocyte antigen presentation to activate specific T cell immune responses in LN., Competing Interests: Declaration of interests All the authors declared no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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