Maturation programs

Immunity 52, 295–312.e11 (2020)

The molecular programs that drive the differentiation of regulatory T (T_reg) cells into tissue resident cells remain unclear. In Immunity, Delacher et al. describe how Klrg1⁺ST2⁺ T_reg cells, a population of tissue resident T_reg cells present in all non-lymphoid tissues, sequentially differentiate from spleen T_reg progenitors. On the basis of ATAC-seq data, Klrg1⁺ST2⁺ T_reg cells from skin, colon and lung are distinct from tissue conventional T cells and lymph node T_reg cells. On the basis of the expression of the transcription factor Nfil3, which is part of a ‘core’ chromatin accessibility signature in Klrg1⁺ST2⁺ T_reg cells, as well as single-cell RNA-seq data, TCR analysis and analysis of postnatal tissue seeding, the authors infer a sequential differentiation of spleen Klrg1^–Nfil3⁺ cells into lymph node Klrg1⁺Nfil3⁺ T_reg cells and then into Klrg1⁺ST2⁺ T_reg cells in tissues. Klrg1^–Batf^–/– precursors do not differentiate into Klrg1⁺ST2⁺ T_reg cells, indicating that the transcription factor Batf enables the development of mature T_reg cells in the tissues.