Small intestine and colon tissue-resident memory CD8+ T cells exhibit molecular heterogeneity and differential dependence on Eomes

Axes of heterogeneity in human tissue‐resident memory T cells

“…21,82,83 TRM also demonstrate sitespecific adaptations and distinct transcriptional signatures across their tissues of residence, including those generated by the same pathogen. [84][85][86] Together, these and other studies highlight the considerable inter-and intra-tissue heterogeneity of TRM, even in the controlled antigenic environment of a specific pathogen-free mouse.…”

“…Elegant studies in mice demonstrate that TRM exhibit a core transcriptional program of residency characterized by expression of genes encoding tissue homing and anchoring receptors discussed above, in addition to suppressed genes associated with recirculation (e.g., Klf2 , S1pr1 , and Ccr7 ) 21,82,83 . TRM also demonstrate site‐specific adaptations and distinct transcriptional signatures across their tissues of residence, including those generated by the same pathogen 84‐86 . Together, these and other studies highlight the considerable inter‐ and intra‐tissue heterogeneity of TRM, even in the controlled antigenic environment of a specific pathogen‐free mouse.…”

Insights into phenotypic and functional CD8+ TRM heterogeneity

“…In fact, recent work has highlighted T RM heterogeneity within tissues and among tissues with differences in surface marker expression, transcriptional changes, functionality, and longevity. 17,26 T RM cells have been identified in almost every human and murine tissue and infiltration and long-term maintenance of these cells in non-lymphoid tissues requires T cells to acclimate to the specific environments that may differ in a broad range of ways, including the availability of nutrients, metabolite composition, cytokine milieu, cell composition, and matrix proteins. It is therefore not surprising that, although T RM cells share a common residency gene-expression signature, they also require tissue-specific acclimatization to persist in and patrol these unique and specialized environments.…”

“…Besides the small intestine and the skin, T RM cells have, for example, been described in the kidney, 17,34 liver, 12,15 salivary gland (SG), 17,35,36 adipose tissue, 17 pancreas, 2 stomach, 2 female reproductive tract, 6 lung, 37,38 and colon. 2,26 Although T RM cells in these organs vary in their durability 6 -ranging from a half-life of 82 days in the uterus to no decay in the salivary gland-they lodge in these tissues for long periods of time, highlighting the necessity of recently migrating T cells to specifically acclimate to their new environment as they become long-lived T RM. 39 Much work has focused on understanding how T RM cells become resident.…”

Tissue-resident memory T cells in gastrointestinal tumors: turning immune desert into immune oasis

“…It is worth noting that Hobit is superior to Blimp-1 in long-term expression of granzyme ( 41 ). Eomes was thought to suppress Trm cell formation, but a recent study revealed that Eomes was essential for Trm maintenance in the intestine but not the colon ( 42 ). Thus, various expression of transcriptional factors determines heterogeneity and existence of Trm cells, which can be altered in case of tumor or infection.…”