Checkpoint Receptor TIGIT Expressed on Tim-1+ B Cells Regulates Tissue Inflammation

Xiao, Sheng; Bod, Lloyd; Pochet, Nathalie; Kota, Savithri Balasubramanian; Hu, Dan; Madi, Asaf; Kilpatrick, Jessica; Shi, Jingwen; Ho, Allen W.; Zhang, Huiyuan; Sobel, Raymond A.; Weiner, Howard L.; Strom, Terry B.; Quintana, Francisco J.; Joller, Nicole; Kuchroo, Vijay K.

doi:10.1016/j.celrep.2020.107892

Cited by 50 publications

(66 citation statements)

References 29 publications

(45 reference statements)

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“…Notably, there was not a major overlap between IL‐10 and TIGIT, which were expressed by distinct populations of TIM‐1 + B cells. TIM‐1 was also found to negatively regulate B cell expression of inflammatory cytokines such as IL‐6, IL‐12, and IL‐23, perhaps enforcing the regulatory balance between Bregs and Beffs 26 . Taken together, these data suggest that while TIM‐1 may not be specific for IL‐10 per se, it may be specific for Bregs that use a variety of mechanisms of action.…”

Section: Regualtory B Cells In Micementioning

confidence: 92%

“…Thus, TIM‐1 regulates an array of potentially inhibitory molecules and may link different “types” of Bregs that utilize distinct mechanisms. Indeed, specific deletion of TIGIT in B cells resulted in spontaneous EAE‐like paralysis and multi‐organ inflammatory cell infiltration, though less severe than that seen in TIM‐1‐BKO mice 26 . Notably, there was not a major overlap between IL‐10 and TIGIT, which were expressed by distinct populations of TIM‐1 + B cells.…”

Section: Regualtory B Cells In Micementioning

confidence: 97%

“…However, in these mice, loss of WT TIM‐1 on B cells may be offset by loss of TIM‐1 on T cells where it plays a costimulatory role 48 . To address this issue, Xiao and colleagues specifically deleted TIM‐1 on B cells (TIM‐1‐BKO) 26 . TIM‐1‐BKO mice older than 10 months developed spontaneous multi‐system autoimmunity characterized by weight loss, dermatitis, rectal prolapse, and EAE‐like paralysis.…”

Section: Regualtory B Cells In Micementioning

confidence: 99%

“…For example, Bregs are still primarily identified by their expression of IL‐10, their best studied suppressive cytokine, leading to a number of different phenotypic "subsets” whose function and lineal relationship to one another are unclear. While a variety of other suppressive regulatory mechanisms have been identified, including PD‐L1, FasL, TIGIT, granzyme B, TGF‐β, and IL‐35, 8,22‐26 the relationship of these cells to IL‐10+ Bregs remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Regulatory B cells: TIM‐1, transplant tolerance, and rejection

Cherukuri

Mohib

Rothstein

2021

Immunological Reviews

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Regulatory B cells (Bregs) ameliorate autoimmune disease and prevent allograft rejection. Conversely, they hinder effective clearance of pathogens and malignancies. Breg activity is mainly attributed to IL‐10 expression, but also utilizes additional regulatory mechanisms such as TGF‐β, FasL, IL‐35, and TIGIT. Although Bregs are present in various subsets defined by phenotypic markers (including canonical B cell subsets), our understanding of Bregs has been limited by the lack of a broadly inclusive and specific phenotypic or transcriptional marker. TIM‐1, a broad marker for Bregs first identified in transplant models, plays a major role in Breg maintenance and induction. Here, we expand on the role of TIM‐1+ Bregs in immune tolerance and propose TIM‐1 as a unifying marker for Bregs that utilize various inhibitory mechanisms in addition to IL‐10. Further, this review provides an in‐depth assessment of our understanding of Bregs in transplantation as elucidated in murine models and clinical studies. These studies highlight the major contribution of Bregs in preventing allograft rejection, and their ability to serve as highly predictive biomarkers for clinical transplant outcomes.

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Section: Regualtory B Cells In Micementioning

confidence: 92%

Section: Regualtory B Cells In Micementioning

confidence: 97%

Section: Regualtory B Cells In Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Regulatory B cells: TIM‐1, transplant tolerance, and rejection

Cherukuri

Mohib

Rothstein

2021

Immunological Reviews

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“…[105][106][107] Similarly, it was recently reported that anti-inflammatory B cells controlled by the commensal flora migrate the gut to the CNS to limit tissue pathology in MS. 108 Interestingly, AHR controls B-cell anti-inflammatory activities. 109,110 Moreover, AHR controls the differentiation and stability of intestinal Tregs, 47,85 and oral administration of the AHR agonist ITE increases the myelin-reactive Treg/Teff ratio and suppresses EAE. 85 These findings suggest that AHR signaling contributes to the anti-inflammatory effects of the commensal flora not only in the gut but also in other tissues, such as the CNS.…”

Section: Modulation Of Inflammation In the Central Nervous System (Cns)mentioning

confidence: 99%

The aryl hydrocarbon receptor and the gut–brain axis

et al. 2021

Self Cite

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The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor initially identified as the receptor for dioxin. Almost half a century after its discovery, AHR is now recognized as a receptor for multiple physiological ligands, with important roles in health and disease. In this review, we discuss the role of AHR in the gut–brain axis and its potential value as a therapeutic target for immune-mediated diseases.

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OMIP‐93: A 41‐color high parameter panel to characterize various co‐inhibitory molecules and their ligands in the lymphoid and myeloid compartment in mice

et al. 2023

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This 41‐color panel has been designed to characterize both the lymphoid and the myeloid compartments in mice. The number of immune cells isolated from organs is often low, whilst an increasing number of factors need to be analyzed to gain a deeper understanding of the complexity of an immune response. With a focus on T cells, their activation and differentiation status, as well as their expression of several co‐inhibitory and effector molecules, this panel also allows the analysis of ligands to these co‐inhibitory molecules on antigen‐presenting cells. This panel enables deep phenotypic characterization of CD4+ and CD8+ T cells, regulatory T cells, γδ T cells, NK T cells, B cells, NK cells, monocytes, macrophages, dendritic cells, and neutrophils. Whilst previous panels have focused on these topics individually, this is the first panel to enable simultaneous analysis of these compartments, thus enabling a comprehensive analysis with a limited number of immune cells/sample size. This panel is designed to analyze and compare the immune response in different mouse models of infectious diseases, but can also be extended to other disease models, for example tumors or autoimmune diseases. Here, we apply this panel to C57BL/6 mice infected with Plasmodium berghei ANKA, a mouse model of cerebral malaria.

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Checkpoint Receptor TIGIT Expressed on Tim-1+ B Cells Regulates Tissue Inflammation

Cited by 50 publications

References 29 publications

Regulatory B cells: TIM‐1, transplant tolerance, and rejection

Regulatory B cells: TIM‐1, transplant tolerance, and rejection

The aryl hydrocarbon receptor and the gut–brain axis

OMIP‐93: A 41‐color high parameter panel to characterize various co‐inhibitory molecules and their ligands in the lymphoid and myeloid compartment in mice

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