Differentiation and Characterization of Tr1 Cells

Chihara, Norio; Madi, Asaf; Karwacz, Katarzyna; Awasthi, Amit; Kuchroo, Vijay K.

doi:10.1002/0471142735.im0327s113

Cited by 36 publications

(46 citation statements)

References 16 publications

(15 reference statements)

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“…This latter set corresponds to the type 1 regulatory cells (Tr1; Roncarolo et al, 2006). Tr1 cells produce high levels of an anti-inflammatory cytokine IL-10, as well as IFN-γ, while undergoing activation in an antigen-specific manner (Chihara et al, 2016; Clemente-Casares et al, 2016). To summarize, the two populations potentially controlling the autoimmune process were present in the islets at all stages, even at 4 wk of age.…”

Section: Resultsmentioning

confidence: 99%

Single-cell RNA sequencing of murine islets shows high cellular complexity at all stages of autoimmune diabetes

Zakharov

Wan

et al. 2020

Journal of Experimental Medicine

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Tissue-specific autoimmune diseases are driven by activation of diverse immune cells in the target organs. However, the molecular signatures of immune cell populations over time in an autoimmune process remain poorly defined. Using single-cell RNA sequencing, we performed an unbiased examination of diverse islet-infiltrating cells during autoimmune diabetes in the nonobese diabetic mouse. The data revealed a landscape of transcriptional heterogeneity across the lymphoid and myeloid compartments. Memory CD4 and cytotoxic CD8 T cells appeared early in islets, accompanied by regulatory cells with distinct phenotypes. Surprisingly, we observed a dramatic remodeling in the islet microenvironment, in which the resident macrophages underwent a stepwise activation program. This process resulted in polarization of the macrophage subpopulations into a terminal proinflammatory state. This study provides a single-cell atlas defining the staging of autoimmune diabetes and reveals that diabetic autoimmunity is driven by transcriptionally distinct cell populations specialized in divergent biological functions.

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Section: Resultsmentioning

confidence: 99%

Single-cell RNA sequencing of murine islets shows high cellular complexity at all stages of autoimmune diabetes

Zakharov

Wan

et al. 2020

Journal of Experimental Medicine

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“…Tr1 cells CD4 + Foxp3 -CD49b + LAG3 + CD226 + Predominantly IL-10; TGF-, CTLA4, and CD226 has been reported in references 17,151 Treg-of-B cells…”

Section: Mechanism Of Suppression and Features Referencementioning

confidence: 99%

The expanding family of noncanonical regulatory cell subsets

Zhao

Feng

Peng

et al. 2019

Journal of Leukocyte Biology

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The overwhelming body of research on regulatory lymphocytes has focused on CD4+ CD25+ Foxp3+ T cells (regulatory T cells); however, the last 5 years have witnessed inspiring progress in our understanding of regulatory B cells, regulatory CD8+ T cells, regulatory γδ cells, and, more recently, regulatory innate lymphoid cells(ILCregs). This review focuses on these so‐called noncanonical regulatory cell subsets. We primarily survey existing information on the phenotype, function, sustaining factors, and clinical value of the 4 best‐characterized non‐CD4 +Foxp3+ T regulatory cells. We then take a brief journey into the advances and challenges associated with next‐generation sequencing technologies and the application of sequencing to the study of noncanonical regulatory cell subsets.

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“…Furthermore, IL‐27 stimulation enhances Tim‐3 expression on Th1 cells, skewing them toward IL‐10‐producing cells . These results pose an interesting question as to whether IL‐27‐driven gene signatures might be a useful tool to identify a gene module regulating effector T cells toward a less immune reactive phenotype by expressing multiple co‐inhibitory molecules and regulatory cytokines, such as IL‐10 …”

Section: Regulatory Cytokines In T‐cell Maintenancementioning

confidence: 99%

Dysregulated T cells in multiple sclerosis

Chihara

2018

Clinical & Exp Neuroim

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Multiple exogenous signals received from cell surface molecules or cytokines play a significant role in altering the host immune response. In chronic autoimmune-mediated diseases, such as multiple sclerosis (MS), immune cells, especially T cells, are involved in the long-term pathophysiology. In the past few decades, mechanisms of pathogenic T-cell involvement at the onset or relapse of disease have been highlighted. However, the factors controlling the disease course have yet to be elucidated because of the complexity of tissue environmental factors. In contrast, dysfunctional or exhausted T cells have been identified as distinct cell lineages in chronic inflammatory diseases, such as cancer or chronic viral infections that show regulatory T cell phenotypes; for example, expressing high levels of co-inhibitory receptors. Regarding cell surface molecule expression, while co-stimulatory molecules promote effector T-cell function, co-inhibitory molecules promote regulatory T-cell function, limiting the inflammatory response. In MS, augmented activation of effector T cells as a result of the impairment of regulatory T-cell function has been implicated. Thus, a comparison between these regulatory T cells in MS and dysfunctional T cells in cancer could provide clues to understand the mechanism of dysregulated T cells, resulting in sustained immune reactions in the long-term disease course of MS. Furthermore, this reveals new immunomodulatory strategies to regain regulatory T-cell function in MS.

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Differentiation and Characterization of Tr1 Cells

Cited by 36 publications

References 16 publications

Single-cell RNA sequencing of murine islets shows high cellular complexity at all stages of autoimmune diabetes

Single-cell RNA sequencing of murine islets shows high cellular complexity at all stages of autoimmune diabetes

The expanding family of noncanonical regulatory cell subsets

Dysregulated T cells in multiple sclerosis

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