The Transmembrane Adaptor Protein LIME Is Essential for Chemokine-Mediated Migration of Effector T Cells to Inflammatiory Sites
- 주제(키워드) chemokine , effector T cells , Lck-interacting transmembrane adaptor 1 , migration
- 주제(기타) Biochemistry & Molecular Biology
- 주제(기타) Cell Biology
- 설명문(일반) [Park, Inyoung; Yun, Yungdae] Ewha Womans Univ, Res Ctr Cellular Homeostasis, Seoul 03760, South Korea; [Son, Myongsun; Ahn, Eunseon; Yun, Yungdae] Ewha Womans Univ, Dept Life Sci, Seoul 03760, South Korea; [Kim, Young-Woong; Kong, Young-Yun] Seoul Natl Univ, Sch Biol Sci, Seoul 08826, South Korea
- 등재 SCIE, SCOPUS, KCI등재
- OA유형 Green Published, gold
- 발행기관 KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000175181
- 본문언어 영어
- Published As http://dx.doi.org/10.14348/molcells.2020.0124
- PubMed https://pubmed.ncbi.nlm.nih.gov/33243936
초록/요약
Lck-interacting transmembrane adaptor 1 (LIME) has been previously identified as a raft-associated transmembrane protein expressed predominantly in T and B lymphocytes. Although LIME is shown to transduce the immunoreceptor signaling and immunological synapse formation via its tyrosine phosphorylation by Lck, a Src-family kinase, the in vivo function of LIME has remained elusive in the previous studies. Here we report that LIME is preferentially expressed in effector T cells and mediates chemokine-mediated T cell migration. Interestingly, in LIME-/- mice, while T cell receptor stimulation-dependent proliferation, differentiation to effector T cells, cytotoxic T lymphocyte (CTL) function and regulatory T lymphocyte (Treg) function were normal, only T cell-mediated inflammatory response was significantly defective. The reduced inflammation was accompanied by the impaired infiltration of leukocytes and T cells to the inflammatory sites of LIME-/- mice. More specifically, the absence of LIME in effector T cells resulted in the reduced migration and defective morphological polarization in response to inflammatory chemokines such as CCL5 and CXCL10. Consistently, LIME-/- effector T cells were found to be defective in chemokine-mediated activation of Rac1 and Rap1, and dysregulated phosphorylation of Pyk2 and Cas. Taken together, the present findings show that LIME is a critical regulator of inflammatory chemokine-mediated signaling and the subsequent migration of effector T cells to inflammatory sites.
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