Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes

TLDR

Tissue‑resident memory T cells localize to pathogen entry portals and provide immediate protection, up‑regulating CD69 and down‑regulating egress molecules, yet a specific transcriptional regulator has not been identified. We found that Hobit, together with Blimp1, is specifically up‑regulated in Trm cells and drives the development of tissue‑resident lymphocytes across skin, gut, liver, kidney, NKT, and liver‑resident NK cells, establishing a universal transcriptional program for tissue retention.

Abstract

Tissue-resident memory T (Trm) cells permanently localize to portals of pathogen entry, where they provide immediate protection against reinfection. To enforce tissue retention, Trm cells up-regulate CD69 and down-regulate molecules associated with tissue egress; however, a Trm-specific transcriptional regulator has not been identified. Here, we show that the transcription factor Hobit is specifically up-regulated in Trm cells and, together with related Blimp1, mediates the development of Trm cells in skin, gut, liver, and kidney in mice. The Hobit-Blimp1 transcriptional module is also required for other populations of tissue-resident lymphocytes, including natural killer T (NKT) cells and liver-resident NK cells, all of which share a common transcriptional program. Our results identify Hobit and Blimp1 as central regulators of this universal program that instructs tissue retention in diverse tissue-resident lymphocyte populations.