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The Transmembrane Adaptor Protein LIME Is Essential for Chemokine-Mediated Migration of Effector T Cells to Inflammatiory Sites

  • Park, Inyoung (Research Center for Cellular Homeostasis, Ewha Womans University) ;
  • Son, Myongsun (Department of Life Science, Ewha Womans University) ;
  • Ahn, Eunseon (Department of Life Science, Ewha Womans University) ;
  • Kim, Young-Woong (School of Biological Sciences, Seoul National University) ;
  • Kong, Young-Yun (School of Biological Sciences, Seoul National University) ;
  • Yun, Yungdae (Research Center for Cellular Homeostasis, Ewha Womans University)
  • Received : 2020.05.29
  • Accepted : 2020.10.12
  • Published : 2020.11.30

Abstract

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.

Keywords

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