T Cell Responses to the Microbiota

Ivanov, Ivaylo I.; Tuganbaev, Timur; Skelly, Ashwin N.; Honda, Kenya

doi:10.1146/annurev-immunol-101320-011829

Cited by 52 publications

(55 citation statements)

References 183 publications

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“…Given their abundance, they have the potential to play an important role in immune response to commensals. Moreover, they are a mixture of Treg and Th17 cells, raising the possibility that the balance within the FA1-specific pool might be relevant to inflammatory and autoimmune disease 5 .…”

Section: Discussionmentioning

confidence: 99%

“…Second, in many cases, the immune cells elicited have a T or B cell receptor specific for an epitope from the strain that elicited them [1][2][3][4]18,19 . These studies have led to the hypothesis that a few "keystone" species dominantly influence the repertoire and function of gut T cells 5,20 .…”

Section: Introductionmentioning

confidence: 99%

“…Immune modulation by the gut microbiome plays an important role in a variety of diseases and therapeutic indications [5][6][7] . As a result, strategies for controlling or redirecting colonist-specific immune responses have considerable therapeutic promise.…”

Section: Introductionmentioning

confidence: 99%

“… ABSTRACT Certain bacterial strains from the microbiome induce a potent, antigen-specific T cell response 1–5 . However, the specificity of microbiome-induced T cells has not been explored at the strain level across the gut community.…”

mentioning

confidence: 99%

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Mapping the T cell repertoire to a complex gut bacterial community

Nagashima

Zhao

Atabakhsh

et al. 2022

Preprint

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Certain bacterial strains from the microbiome induce a potent, antigen-specific T cell response. However, the specificity of microbiome-induced T cells has not been explored at the strain level across the gut community. Here, we colonize germ-free mice with a complex defined community (97 or 112 bacterial strains) and profile T cell responses to each strain individually. Unexpectedly, the pattern of T cell responses suggests that many T cells in the gut repertoire recognize multiple bacterial strains from the community. We constructed T cell hybridomas from 92 T cell receptor (TCR) clonotypes; by screening every strain in the community against each hybridoma, we find that nearly all of the bacteria-specific TCRs exhibit a one-to-many TCR-to-strain relationship, including 13 abundant TCR clonotypes that are polyspecific for 18 Firmicutes in the community. By screening three pooled bacterial genomic libraries against 13 pooled hybridomas, we discover that they share a single target: a conserved substrate-binding protein (SBP) from an ABC transport system. Treg and Th17 cells specific for an epitope from this protein are abundant in community-colonized and specific-pathogen-free mice. Our work reveals that T cell recognition of Firmicutes is focused on a widely conserved cell-surface antigen, opening the door to new therapeutic strategies in which colonist-specific immune responses are rationally altered or redirected.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Mapping the T cell repertoire to a complex gut bacterial community

Nagashima

Zhao

Atabakhsh

et al. 2022

Preprint

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“… 4 Gut microbiota, which emerges as an important regulator in human health and diseases, has a critical role in regulating T cell functions. 5 Gut microbiota modulates CD4 + T cell metabolic profiles to regulate immune responses, especially through bacteria-derived metabolites. 6 T cell metabolic alteration has been linked with the pathogenesis of autoimmune disorders, and manipulation of metabolic pathways becomes the potential therapy for treating these diseases.…”

Section: Introductionmentioning

confidence: 99%

CD4+ T cell metabolism, gut microbiota, and autoimmune diseases: implication in precision medicine of autoimmune diseases

Yang

Cong

2022

Precision Clinical Medicine

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CD4+ T cells are critical to the development of autoimmune disorders. Glucose, fatty acids, and glutamine metabolisms are the primary metabolic pathways in immune cells, including CD4+ T cells. The distinct metabolic programs in CD4+ T cell subsets are recognized to reflect the bioenergetic requirements, which are compatible with their functional demands. Gut microbiota affects T cell responses by providing a series of antigens and metabolites. Accumulating data indicate that CD4+ T cell metabolic pathways underlie aberrant T cell functions, thereby regulating the pathogenesis of autoimmune disorders, including inflammatory bowel diseases, systemic lupus erythematosus, and rheumatoid arthritis. Here, we summarize the current progress of CD4+ T cell metabolic programs, gut microbiota regulation of T cell metabolism, and T cell metabolic adaptions to autoimmune disorders to shed light on potential metabolic therapeutics for autoimmune diseases.

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Specificity and function of T cell subset identities using single‐cell sequencing

Liu

Zhu

Wang

2023

Clinical and Translational Dis

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T cells, with numerous classifications, are vital components of the adaptive immune system, which function to maintain homeostasis to protect against pathogens. With the rapid development of single‐cell RNA sequencing (scRNA‐seq), the specificity and functions of high‐resolution characterizations and identities of T cells are continuously explored and discovered. The exact T cell identities provide new insights for deeply understanding the heterogeneity of T cells and for the identification of previously unrecognized cell subsets. The accuracy and specificity of T cell cluster and annotation are critical and important in scRNA‐seq analyses, even though the characters and numbers of T cell marker gene panels (MGPs) are to be furthermore improved and uncovered. In order to initiate the discussion on identities of T cell subsets/clusters and impacts of identity specificity in the understanding of immune function, the present review systematically summarized the T cell identities of MGPs and functional characteristics of distinct T cell identities in the scRNA‐seq analysis. We also discussed the critical gene differences among panels across T cell subsets, cell functional states, tissue types, and diseases, with a special focus on the significance and potential values of T cell MGP accuracy and specificity in clinical applications. We hope that the precise knowledge of T cell subsets/clusters benefit decision designs and makings of biomarker discoveries and therapeutic strategies to improve the outcomes of patients.

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T Cell Responses to the Microbiota

Cited by 52 publications

References 183 publications

Mapping the T cell repertoire to a complex gut bacterial community

Mapping the T cell repertoire to a complex gut bacterial community

CD4+ T cell metabolism, gut microbiota, and autoimmune diseases: implication in precision medicine of autoimmune diseases

Specificity and function of T cell subset identities using single‐cell sequencing

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