Krüppel-like factor 2 regulates trafficking and homeostasis of γδ T cells

γδ T cells are generated in the thymus and traffic to secondary lymphoid organs and epithelial surfaces, where they regulate immune responses. αβ T cells require sphingosine 1-phosphate receptor type 1 (S1P ₁) and CD62L for thymic emigration and circulation through secondary lymphoid organs. Both of these genes are regulated by the transcription factor Krüppel-like factor 2 (KLF2) in conventional αβ T cells. It is unclear if γδ T cells use similar mechanisms. In this study, we show that thymic γδ T cells express S1P₁ and that it is regulated by KLF2. Furthermore, KLF2 and S1P₁-deficient γδ T cells accumulate in the thymus and fail to populate the secondary lymphoid organs or gut, in contrast to the expectation from published work. Interestingly, KLF2 but not S1P₁ deficiency led to the expansion of a usually rare population of CD4⁺ promyelocytic leukemia zinc finger⁺ "γδ NKT" cells. Thus, KLF2 is critically important for the homeostasis and trafficking of γδ T cells.