摘要：SummaryFoxp3+regulatory T cells (Tregs) are critical mediators of peripheral tolerance and immune homeostasis and exert tissue-specific functions. In many nonlymphoid tissues, Tregs show enriched expression of the IL-33 receptor ST2. Through comprehensive profiling of murine ST2+and ST2-Tregs, we found that Treg transcriptomes and phenotypes formed a hierarchical relationship across tissues. Only a small core signature distinguished ST2+Tregs from ST2-Tregs across all tissues, and differences in transcriptional profiles were predominantly tissue-specific. We also identified unique, highly proliferative, circulating ST2+Tregs with high migratory potential. In adoptive transfers, both ST2+and ST2-Tregs seeded various host tissues and demonstrated plasticity in ST2 expression. Furthermore, Tregs from donor lungs were differentially recovered from host nonlymphoid tissues in an IL-33-dependent manner. In summary, our work identified tissue residency rather than ST2 expression as a primary driver of tissue Treg identity and highlights the unique, tissue-specific adaption of ST2+Tregs.Graphical abstractDisplay OmittedHighlights•Tissue of residency rather than ST2 expression is a primary driver of Treg identity•A small core signature distinguishes ST2+Tregs from ST2-Tregs across tissues•Circulating ST2+Tregs have diverse chemokine receptor profiles•Plasticity of ST2 expression on transferred Tregs occurs in a tissue-specific mannerImmunology; Components of the immune system; Transcriptomics
