Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity

Christo, Susan N; Evrard, Maximilien; Park, Simone L.; Gandolfo, Luke C.; Burn, Thomas N.; Fonseca, Raíssa; Newman, Dane M.; Alexandre, Yannick O.; Collins, Nicholas; Zamudio, Natasha; Souza-Fonseca-Guimarães, Fernando; Pellicci, Daniel G.; Chisanga, David; Shi, Wei; Bartholin, Laurent; Belz, Gabrielle T.; Huntington, Nicholas; Lucas, Andrew; Lucas, Michaela; Mueller, Scott N.; Heath, William R.; Ginhoux, Florent; Speed, Terence P.; Carbone, Francis R.; Kallies, Axel; Mackay, Laura K.

doi:10.1038/s41590-021-01004-1

Cited by 133 publications

(159 citation statements)

References 49 publications

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“…To determine the impact of TGF-β on RNA sequencing data of spleen CD8 + T cells cultured in β. We observed that TGF-β not only induced expressio but also strongly upregulated expression of Adgrg1 (Fig [29] in the skin and small intestine [30]. TGF-β can also establish part of the residency-specific transcriptional profile of T RM cells, including the induction of Itgae/CD103 [31].…”

Section: Cd8 + Trm Cell-inducing Factors Regulate Adgrg1/gpr56 Expressionmentioning

confidence: 74%

“…Pathogen-specific T RM cells express a multitude of inhibitory receptors including PD-1, TIM-3, LAG-3 and CD39 that can restrain T RM cell-driven immune responses [33]. Interestingly, CD103 + T RM cells appear to be under stronger regulation by inhibitory receptors than CD103 − T RM cells [30]. In line with these findings, we also found that the inhibitory receptor GPR56 is responsive to TGF-β suggesting elevated expression of this receptor on CD103 + T RM cells compared to CD103 − T RM cells.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, GPR56 does not appear to essentially tribute to TRM-cell differentiation in the Listeria-OVA infection model and the regula of granzyme B expression in Listeria-OVA specific TRM cells. TGF-β has been shown to specifically promote the development or mainten TRM cells in vivo [29] in the skin and small intestine [30]. TGF-β can also establish the residency-specific transcriptional profile of TRM cells, including the induc Itgae/CD103 [31].…”

Section: Adgrg1/gpr56 Does Not Regulate Cytotoxic Function Of Cd8 + Trm Cellsmentioning

confidence: 99%

“…Virus-specific CD8 + T cells recognizing the dominant e GP33-41 were detected using tetramers at different locations and time points after in We found that GPR56 was not essential for the formation of GP33-41 + CD8 + T cells in liver, and small intestine at effector (day 8) and memory time points (day 30+) after infection (Figure 3B). Expression of IL-7Rα chain (CD127) in conjunction with KLR TGF-β has been shown to specifically promote the development or maint TRM cells in vivo [29] in the skin and small intestine [30]. TGF-β can also establi the residency-specific transcriptional profile of TRM cells, including the ind Itgae/CD103 [31].…”

Section: Adgrg1/gpr56 Is Dispensable For the Development Of Cd8 + Trm Cellsmentioning

confidence: 99%

“…Analysis of the act cells indicated the specific deletion of thi GPR56 was analyzed on virus-specific C with LCMV (Figure 3A). Virus-specific as been shown to specifically promote the development or maintenance of ivo [29] in the skin and small intestine [30]. TGF-β can also establish part of -specific transcriptional profile of TRM cells, including the induction of 31].…”

Section: Adgrg1/gpr56 Is Dispensable For the Dmentioning

confidence: 99%

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The Inhibitory Receptor GPR56 (Adgrg1) Is Specifically Expressed by Tissue-Resident Memory T Cells in Mice But Dispensable for Their Differentiation and Function In Vivo

Hsiao

Kragten

Piao

et al. 2021

Cells

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Tissue-resident memory T (TRM) cells with potent antiviral and antibacterial functions protect the epithelial and mucosal surfaces of our bodies against infection with pathogens. The strong proinflammatory activities of TRM cells suggest requirement for expression of inhibitory molecules to restrain these memory T cells under steady state conditions. We previously identified the adhesion G protein-coupled receptor GPR56 as an inhibitory receptor of human cytotoxic lymphocytes that regulates their cytotoxic effector functions. Here, we explored the expression pattern, expression regulation, and function of GPR56 on pathogen-specific CD8+ T cells using two infection models. We observed that GPR56 is expressed on TRM cells during acute infection and is upregulated by the TRM cell-inducing cytokine TGF-β and the TRM cell-associated transcription factor Hobit. However, GPR56 appeared dispensable for CD8+ T-cell differentiation and function upon acute infection with LCMV as well as Listeria monocytogenes. Thus, TRM cells specifically acquire the inhibitory receptor GPR56, but the impact of this receptor on TRM cells after acute infection does not appear essential to regulate effector functions of TRM cells.

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Section: Cd8 + Trm Cell-inducing Factors Regulate Adgrg1/gpr56 Expressionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Adgrg1/gpr56 Does Not Regulate Cytotoxic Function Of Cd8 + Trm Cellsmentioning

confidence: 99%

Section: Adgrg1/gpr56 Is Dispensable For the Development Of Cd8 + Trm Cellsmentioning

confidence: 99%

Section: Adgrg1/gpr56 Is Dispensable For the Dmentioning

confidence: 99%

See 3 more Smart Citations

The Inhibitory Receptor GPR56 (Adgrg1) Is Specifically Expressed by Tissue-Resident Memory T Cells in Mice But Dispensable for Their Differentiation and Function In Vivo

Hsiao

Kragten

Piao

et al. 2021

Cells

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Intestinal CD8⁺ tissue‐resident memory T cells: From generation to function

Cheng

Becattini

2022

Eur J Immunol

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Tissue‐resident memory T cells (Trm), and particularly the CD8+ subset, have been shown to play a pivotal role in protection against infections and tumors. Studies in animal models and human tissues have highlighted that, while a core functional program is shared by Trm at all anatomical sites, distinct tissues imprint unique features through specific molecular cues. The intestinal tissue is often the target of pathogens for local proliferation and penetration into the host systemic circulation, as well as a prominent site of tumorigenesis. Therefore, promoting the formation of Trm at this location is an appealing therapeutic option. The various segments composing the gastrointestinal tract present distinctive histological and functional characteristics, which may reflect on the imprinting of unique functional features in the respective Trm populations. What these features are, and whether they can effectively be harnessed to promote local and systemic immunity, is still under investigation. Here, we review how Trm are generated and maintained in distinct intestinal niches, analyzing the required molecular signals and the models utilized to uncover them. We also discuss evidence for a protective role of Trm against infectious agents and tumors. Finally, we integrate the knowledge obtained from animal models with that gathered from human studies.

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Tissue‐resident memory T (T_RM) cells: Front‐line workers of the immune system

2023

Self Cite

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Tissue‐resident memory T (TRM) cells play a vital role in local immune protection against infection and cancer. The location of TRM cells within peripheral tissues at sites of pathogen invasion allows for the rapid detection and elimination of microbes, making their generation an attractive goal for the development of next‐generation vaccines. Here, we discuss differential requirements for CD8+ TRM cell development across tissues with implications for establishing local prophylactic immunity, emphasizing the role of tissue‐derived factors, local antigen, and adjuvants on TRM cell generation in the context of vaccination.

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Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity

Cited by 133 publications

References 49 publications

The Inhibitory Receptor GPR56 (Adgrg1) Is Specifically Expressed by Tissue-Resident Memory T Cells in Mice But Dispensable for Their Differentiation and Function In Vivo

The Inhibitory Receptor GPR56 (Adgrg1) Is Specifically Expressed by Tissue-Resident Memory T Cells in Mice But Dispensable for Their Differentiation and Function In Vivo

Intestinal CD8⁺ tissue‐resident memory T cells: From generation to function

Tissue‐resident memory T (T_RM) cells: Front‐line workers of the immune system

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Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity

Cited by 133 publications

References 49 publications

The Inhibitory Receptor GPR56 (Adgrg1) Is Specifically Expressed by Tissue-Resident Memory T Cells in Mice But Dispensable for Their Differentiation and Function In Vivo

The Inhibitory Receptor GPR56 (Adgrg1) Is Specifically Expressed by Tissue-Resident Memory T Cells in Mice But Dispensable for Their Differentiation and Function In Vivo

Intestinal CD8+ tissue‐resident memory T cells: From generation to function

Tissue‐resident memory T (TRM) cells: Front‐line workers of the immune system

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Product

Resources

About

Intestinal CD8⁺ tissue‐resident memory T cells: From generation to function

Tissue‐resident memory T (T_RM) cells: Front‐line workers of the immune system