Cho Hyoung-Soo, Ha Soyoung, Shin Hyun Mu, Reboldi Andrea, Hall Jason A, Huh Jun R, Usherwood Edward J, Berg Leslie J
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01605.
Department of Immunology, Harvard Medical School, Boston, MA 02115.
Immunohorizons. 2020 Feb 7;4(2):57-71. doi: 10.4049/immunohorizons.1900093.
The Tec kinase IL-2-inducible T cell kinase (ITK) regulates the expression of TCR-induced genes. T cell responses are impaired but not absent. ITK inhibition prevented colitis disease progression and impaired T cell migration to the colon in mice. To examine the function of ITK in T cell migration to the intestine, we examined the number of gut T cells in mice and then evaluated their expression of gut-homing receptors. Combined with in vitro murine T cell stimulation and in vivo migration assay using congenic B6 mice, we demonstrated an essential role for ITK in T cell migration to the intestine in mice. Reconstitution of mouse CD8 T cells with IFN regulatory factor 4 restored gut-homing properties, providing mechanistic insight into the function of ITK-mediated signaling in CD8 T cell migration to the intestinal mucosa in mice.
酪氨酸激酶白细胞介素-2诱导型T细胞激酶(ITK)调节T细胞受体诱导基因的表达。T细胞反应受损但并非完全缺失。ITK抑制可防止小鼠结肠炎疾病进展,并损害T细胞向结肠的迁移。为了研究ITK在T细胞向肠道迁移中的功能,我们检测了小鼠肠道T细胞的数量,然后评估了它们肠道归巢受体的表达。结合体外小鼠T细胞刺激和使用同源B6小鼠的体内迁移试验,我们证明了ITK在小鼠T细胞向肠道迁移中起重要作用。用干扰素调节因子4重建小鼠CD8 T细胞可恢复肠道归巢特性,为ITK介导的信号在小鼠CD8 T细胞向肠黏膜迁移中的功能提供了机制性见解。