Distinct mechanisms govern resident memory T cell differentiation and survival in different tissues

Abstract

Abstract Tissue-resident memory T (Trm) cells are a recently defined population of memory T cells that persist at the site of previous infection and contribute to protective local immunity. Trm cells have been identified in both epithelial and solid organs; however, despite their ubiquity, they share molecular commonalities that are distinct from circulating memory T cells. Therefore, we sought to explore the transcriptional regulation of Trm cells in a number of different organs. Our earlier data demonstrated that Trm cells share a core transcriptional signature regulated by the two related transcription factors Hobit and Blimp1. Here we show that Trm cells also have distinct molecular requirements according to anatomic location. While Hobit was uniquely required for the development of Trm cells in all organs tested, Blimp1 was required in some organs, but dispensable in others. Similar to Blimp1, the T-box transcription factor T-bet was also required for Trm cell development in only a subset of organs. This differential transcription factor dependency was linked to distinct cytokine requirements for Trm cell development in different organs. Trm cell defects were enhanced in the absence of multiple transcription factors, suggesting functional redundancy and implicating a role for distinct transcriptional networks as drivers of Trm cell development in different organs. Together, these data demonstrate the adaptation of Trm cells to specific tissue microenvironments and highlight the importance of studying these cells in a variety of organs.