Good news!
"We owe a lot to tissue resident memory T cells (TRM). These specialized immune cells are among the body's first responders to disease.
Rather than coursing through the bloodstream—as many T cells do—our TRM cells specialize in defending specific organs. They battle viruses, breast cancer, liver cancer, melanomas, and many other health threats. ...
shown that a greater density of TRM cells is linked to better survival outcomes in lung cancer patients. ...
discovered the cellular driver that leads to TRM cell development. Their findings ... offer a potential way to boost TRM cell numbers to better fight disease.
"We found a new molecule that is likely to play an important role in the development and function of TRM cells," ...
In a previous study ... found that TRM cells are studded with a membrane receptor molecule called G-protein coupled receptor 25 (GPR25). This high level of GPR25 expression is unusual. ...
In their new study, the ... scientists are the first to show that GPR25 is induced by a signaling molecule called TGF-β. GPR25 sustains TGF-β downstream signaling, which promotes a process called differentiation, during which a regular memory T cell transforms into a TRM cell. ...
confirmed the importance of GPR25. ... mice with GPR25 deficiency don't sustain TGF-β signaling properly and cannot maintain a functional population of TRM cells. Further experiments suggested that tweaking GPR25 activity could work as a way to enhance or suppress TRM cell activity. ..."
From the editor's summary and abstract:
"Editor’s summary
Effective immunity against secondary infection and tumor rechallenge depends on tissue-resident memory CD8 T (TRM) cells. Feng et al. uncovered the key role of G protein–coupled receptor GPR25 in promoting TRM cell differentiation instead of an effector memory phenotype.
Tracking of T cell differentiation into TRM cells upon tumor rechallenge, viral reinfection, and parabiosis revealed that GPR25 acts downstream of TGF-β signaling to promote TRM cell differentiation and tissue residency in the lung and liver. GPR25 expression was induced by TGF-β and maintained a T cell factor 1 (TCF1)–dependent stem-like TRM cell program, highlighting its potential as a target to augment antiviral and antitumor TRM cell responses. ...
Abstract
Tissue-resident memory CD8 T (TRM) cells provide critical antiviral and antitumor immunity, but the molecular pathways guiding their development are not fully defined.
Here, we identify the G protein–coupled receptor GPR25, induced by TGF-β signaling, as a regulator of TRM cell formation.
Using adoptive transfer, we found that Gpr25-deficient T cells infiltrated tissues normally after viral infection but failed to efficiently develop into TRM cells.
In a tumor challenge model, Gpr25 deficiency impaired TRM cell expansion and tumor control. Single-cell transcriptomics revealed defective acquisition of stem-like TRM cell features, including expression of T cell factor 1 (TCF1).
After antigen rechallenge, Gpr25-deficient TRM cells showed impaired secondary TRM cell differentiation and maintenance.
Moreover, Gpr25-deficient T cells displayed negative enrichment of TGF-β signature genes and impaired responses to TGF-β, indicating that GPR25 enhances TGF-β signaling to promote TRM cell development.
Our findings suggest that modulating GPR25 function may provide a therapeutic strategy to improve TRM cell responses in infection and cancer."
LJI scientists discover how T cells transform to defend our organs (original news release) "Future drugs could target specialized T cells to help the body fight tumors, infections, and more"
GPR25 promotes the formation of lung and liver tissue-resident memory CD8 T cells (no public access)
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