Human TIM-3-CD22 interaction regulates innate immune activation in autoimmune diseases 4325
Year: 2025
Type: article
Abstract: Description Immune co-inhibitory receptors are essential for maintaining immune cell homeostasis. TIM-3, initially identified on terminally differentiated T cells, is now recognized as being expressed on various immune cell types, including myeloid cells. However, its regulatory mechanisms in myeloid cells, particularly in autoimmune diseases, remain poorly understood. Germline loss-of-function mutations in TIM-3 have been linked to subcutaneous panniculitis-like T cell lymphoma (SPTCL), often associated with autoimmune disorders. Reduced TIM-3 surface expression on myeloid cells in multiple sclerosis (MS) patients further underscores its role in immune regulation. Using CRISPR-Cas9 to knock out TIM-3 in human primary myeloid cells, we observed increased inflammasome activation and elevated chemokine secretion (CXCL9, CXCL10), promoting a pro-inflammatory microenvironment. Phosphoproteome profiling identified key mediators of TIM-3 signaling, including LYN, HSP60, NFκB, and MAP kinase pathways. Co-immunoprecipitation and mass spectrometry revealed CD22 and LYN as TIM-3 interaction partners. Interestingly, CD22, a co-inhibitory receptor typically found on B cells, was also detected on microglia and DC/macrophages in human, where it appears to function as an inhibitory regulator by modulating immune responses. These findings highlight the TIM-3-CD22-LYN axis as a novel pathway in immune regulation and suggest it as a promising therapeutic target for autoimmune diseases like SPTCL and MS. Funding Sources Supported by the National Multiple Sclerosis Society (NMSS) (Harry Weaver Award: JF-2208-40314) and Race to Erase MS Young investigator award to T.S.S. Topic Categories Immune Mechanisms of Human Disease (HUM)
Source: The Journal of Immunology
Authors: Tomokazu S. Sumida, Alice Yi
Institution: Yale University
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416448445
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