T cells in ARAP-deficient mice present defective T cell receptor signaling and reduced severity in an experimentally-induced autoimmune disease

We previously reported a novel adaptor protein, ARAP, required for T cell receptor signaling and integrin-mediated adhesion. The present study investigates further the role of ARAP in T cell biology using mice with an ARAP gene deficiency. Similar to wild-type mice, ARAP-deficient mice participate i...

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Bibliographic Details
Main Authors: Jee-Hae Kim, Seung Hee Jung, Chohee Park, Jong Ran Lee
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1556616/full
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Summary:We previously reported a novel adaptor protein, ARAP, required for T cell receptor signaling and integrin-mediated adhesion. The present study investigates further the role of ARAP in T cell biology using mice with an ARAP gene deficiency. Similar to wild-type mice, ARAP-deficient mice participate in normal breeding and immune cell development. Similar defects were observed in the T cell receptor signaling and adhesion of ARAP-deficient mice, as shown in previous studies investigating ARAP-suppressed Jurkat T cells. ARAP deficiencies analyzed in vivo presented a less severe clinical course of experimental autoimmune encephalomyelitis (EAE) following immunization of mice with the myelin oligodendrocyte glycoprotein (MOG). Serum levels of MOG-specific antibodies and IFN-γ were also reduced in ARAP-deficient EAE mice compared to wild-type EAE mice. Moreover, adoptive transfer of ARAP-deficient T cells induced less severe EAE in recombination-activating gene 1-deficient mice than wild-type T cell transfer. These results strongly suggest that ARAP positively regulates T cell function, while ARAP deficiency in T cells reduces the severity and incidence of EAE.
ISSN:1664-3224