The gut microbiota promotes distal tissue regeneration via RORγ+ regulatory T cell emissaries

Hanna, Bola S.; Wang, Gang; Galván-Peña, Silvia; Mann, Alexander O.; Ramirez, Ricardo N.; Muñoz-Rojas, Andrés R.; Smith, Kathleen M.; Wan, Min; Benoist, Christophe; Mathis, Diane

doi:10.1016/j.immuni.2023.01.033

Cited by 52 publications

(31 citation statements)

References 105 publications

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“…This trafficking was blocked by FTY720 treatment, suggesting a role for S1PR1 signaling in T cell exit from the gut 89 . A similar approach demonstrated that Rorγt+ regulatory T cell migration from the colon to injured skeletal muscle was blocked by FTY720 90 . In a study that relied on injection of cells into the footpad, S1pr1 −/− naïve T cells, effector T cells treated with an S1PR1 antagonist, S1pr4 −/− naïve T cells, and effector T cells treated with an S1PR4 antagonist trafficked poorly to the downstream popliteal lymph node 91 …”

Section: S1p Signaling In Exit From Non‐lymphoid Organs During An Imm...mentioning

confidence: 86%

“…89 A similar approach demonstrated that Rorγt+ regulatory T cell migration from the colon to injured skeletal muscle was blocked by FTY720. 90 In a study that relied on injection of cells into the footpad, S1pr1 −/− naïve T cells, effector T cells treated with an S1PR1 antagonist, S1pr4 −/− naïve T cells, and effector T cells treated with an S1PR4 antagonist trafficked poorly to the downstream popliteal lymph node. 91 Taking the converse approach, forced expression of S1pr1 by retroviral transduction strongly limited effector T cell accumulation in inflamed tissues, without affecting their initial recruitment.…”

Section: Role Of S1p Signaling In T Cell Exit From Nonlymphoid Tissuesmentioning

confidence: 99%

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Get me out of here: Sphingosine 1‐phosphate signaling and T cell exit from tissues during an immune response

Hallisey

Schwab

2023

Immunological Reviews

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SummaryDuring an immune response, the duration of T cell residence in lymphoid and non‐lymphoid tissues likely affects T cell activation, differentiation, and memory development. The factors that govern T cell transit through inflamed tissues remain incompletely understood, but one important determinant of T cell exit from tissues is sphingosine 1‐phosphate (S1P) signaling. In homeostasis, S1P levels are high in blood and lymph compared to lymphoid organs, and lymphocytes follow S1P gradients out of tissues into circulation using varying combinations of five G‐protein coupled S1P receptors. During an immune response, both the shape of S1P gradients and the expression of S1P receptors are dynamically regulated. Here we review what is known, and key questions that remain unanswered, about how S1P signaling is regulated in inflammation and in turn how S1P shapes immune responses.

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Section: S1p Signaling In Exit From Non‐lymphoid Organs During An Imm...mentioning

confidence: 86%

Section: Role Of S1p Signaling In T Cell Exit From Nonlymphoid Tissuesmentioning

confidence: 99%

Get me out of here: Sphingosine 1‐phosphate signaling and T cell exit from tissues during an immune response

Hallisey

Schwab

2023

Immunological Reviews

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“…Therefore, the microbial profiles shift in present study maybe one of the causes which influence the therapeutic effect of OVV-gp33 treatment in advanced stage of CRC. Specific microbial signals induce the differentiation of T cells which is crucial for intestinal hemostasis [32]. Here, depletion of the intestinal microbiota resulted in impaired host immune responses, prevented CD8 + T-cell activation and increased ratio of Treg cells.…”

Section: Discussionmentioning

confidence: 99%

Intestinal microbiota modulates the anti-tumor effect of oncolytic virus vaccine in colorectal cancer

Chen

Wang

Qin

et al. 2023

Preprint

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BackgroundImmunotherapy such as oncolytic virus has become a powerful cancer treatment but only a part of cancer patients can benefit from it, especially to advanced-stage cancer patients are required new therapeutic strategies to facilitate extended survival. Intestinal microbiota may contribute to colorectal cancer (CRC) carcinogenesis and response to immunotherapy. However, whether and how the modulating effect of intestinal microbiota on oncolytic virus vaccine (OVV) in CRC remains to be investigated.MethodsWe generated a MC38-gp33 CRC mouse model and treated with OVV-gp33 in early- and advanced-stages. Probiotics, fecal microbiota transplantation (FMT) and antibiotics (ABX) were treated to regulate the microbial composition of CRC mice of advanced stage. The tumor growth rate and survival time of mice were recorded. 16S rDNA sequencing analyzed the microbial composition and flow cytometry detected the T cells subsets activity.ResultsOVV-gp33 treatment led to inhibited tumor growth and prolonged survival in the early stage of CRC but did not have a significant effect on the advanced stage of CRC. Moreover, 16S rDNA sequence analysis and flow cytometry showed significant differences in intestinal microbiota composition, microbial metabolites and T-cell subsets in early- and advanced-stage CRC. Probiotic and FMT treatment significantly enhanced the antitumor effect of OVV in advanced stage of CRC with an increased abundance of activated CD8+T cells and a decreased ratio of Treg cells, while depletion of the microbiota by ABX eliminated the antitumor activity of OVV with decreased CD8+T-cell activation and upregulated Treg cells.ConclusionsThese results indicate that intestinal microbiota and microbial metabolites play an important role in the OVV antitumor effect in CRC, furthermore, altering the intestinal microbiota composition can modulate the antitumor and immunomodulatory effect of OVV in CRC.

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“…Harvard Medical School (HMS) researchers have discovered that a class of regulatory T cells (Tregs) made in the gut play a role in repairing injured muscles and mending damaged livers. (See Hanna et al, 2023. )…”

mentioning

confidence: 99%

“…Further, Bola Hanna, PhD, a research fellow in immunology at HMS, and colleagues found that gut microbes fuel the production of Tregs. (See Hanna et al, 2023. )…”

mentioning

confidence: 99%

Gut Microbes Help to Repair Injured Muscles and Damaged Livers

2023

Lippincott's Bone and Joint Newsletter

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The gut microbiota promotes distal tissue regeneration via RORγ+ regulatory T cell emissaries

Cited by 52 publications

References 105 publications

Get me out of here: Sphingosine 1‐phosphate signaling and T cell exit from tissues during an immune response

Get me out of here: Sphingosine 1‐phosphate signaling and T cell exit from tissues during an immune response

Intestinal microbiota modulates the anti-tumor effect of oncolytic virus vaccine in colorectal cancer

Gut Microbes Help to Repair Injured Muscles and Damaged Livers

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