Implications of regulatory T cells in non-lymphoid tissue physiology and pathophysiology

Malko, Darya; Elmzzahi, Tarek; Beyer, Marc

doi:10.3389/fimmu.2022.954798

Cited by 9 publications

(6 citation statements)

References 212 publications

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“…Tregs are essential for the maintenance of self‐tolerance and immune homeostasis. They can cause the body to lose peripheral tolerance and lead to autoimmune diseases 35,36 . Although there is a consensus on the dysfunction of Tregs in SSc, the quantification of Tregs showed several paradoxical results, which may be related to heterogeneous factors of the studies, such as the enrolling phenotype of patients and the detection markers of Treg 32 .…”

Section: Discussionmentioning

confidence: 99%

“…They can cause the body to lose peripheral tolerance and lead to autoimmune diseases. 35,36 Although there is a consensus on the dysfunction of Tregs in SSc, the quantification of Tregs showed several paradoxical results, which may be related to heterogeneous factors of the studies, such as the enrolling phenotype of patients and the detection markers of Treg. 32 Interestingly, MacDonald et al 14 increased Tfh2 were found in the SSc group, with similar proportions of total Tfh, Tfh17, and activated Tfh with activation marker PD-1.…”

Section: F I G U R E 2 Altered Expression Of Cd4 +mentioning

confidence: 99%

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Alterations in peripheral T‐ and B‐cell subsets in patients with systemic sclerosis

Wu,

Zhang,

Lin

et al. 2024

Int J of Rheum Dis

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ObjectivesTo determine the alteration of peripheral T and B cell subsets in patients with systemic sclerosis (SSc) and to evaluate their correlation with the progression of SSc.MethodsWe recruited 47 SSc patients and 45 healthy controls (HCs) in this study. Demographic and clinical data were then collected. Flow cytometry was used to detect the proportions of 44 different T and B cell subsets in circulating blood.ResultsThe proportion of total B cells (p = .043) decreased in SSc patients, together with similar frequencies of total T cells, CD4+ T cells, and CD8+ T cells in both groups. Several subsets of T and B cells differed significantly between these two groups. Follicular helper T cells‐1 (Tfh1) (p < .001), helper T cells‐1 (Th1) (p = .001), regulatory T cells (Treg) (p = .004), effector memory CD8+ T cells (p = .041), and cytotoxic T cells‐17 (Tc17) (p = .01) were decreased in SSc patients. Follicular helper T cells‐2 (Tfh2) (p = .001) and, helper T cells‐2 (Th2) (p = .001) levels increased in the SSc group. Regulatory B cells (Breg) (p = .015) were lower in the SSc group, together with marginal zone (MZ) B cells (p < .001), memory B cells (p = .001), and non‐switched B cells (p = .005). The modified Rodnan skin score (mRSS) correlated with helper T cells‐17 (Th17) (r = −.410, p = .004), Tfh1 (r = −.321, p = .028), peripheral helper T cells (Tph) (r = −.364, p = .012) and plasma cells (r = −.312, p = .033).ConclusionsThe alterations in T and B cells implied immune dysfunction, which may play an essential role in systemic sclerosis.

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Section: Discussionmentioning

confidence: 99%

Section: F I G U R E 2 Altered Expression Of Cd4 +mentioning

confidence: 99%

Alterations in peripheral T‐ and B‐cell subsets in patients with systemic sclerosis

Wu,

Zhang,

Lin

et al. 2024

Int J of Rheum Dis

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“…Tregs are present within the non-lymphoid tissues, such as adipose tissue, muscle, and skin, and they are thought to play an important role in tissue homeostasis (39, 40). The inflamed lung tissues during allergic airway inflammation are heavily infiltrated with Tregs; however, the mechanisms through which they control lung inflammation has not thoroughly been examined.…”

Section: Discussionmentioning

confidence: 99%

Single cell analysis uncovers striking cellular heterogeneity of lung infiltrating Tregs during eosinophilic vs. neutrophilic allergic airway inflammation

Iamsawat,

Yu,

Kim

et al. 2023

Preprint

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Allergic airway inflammation is a chronic inflammatory condition resulting from uncontrolled immune responses to environmental antigens. While it is well-established that allergic immune responses exhibit a high degree of diversity, driven by primary effector cell types like eosinophils, neutrophils, or CD4 T cells with distinct effector signatures, the exact mechanisms responsible for such pathogenesis remain largely elusive. Foxp3+ regulatory T cells (Treg) is an essential immune regulator during chronic inflammation including allergic airway inflammation. Emerging evidence suggests that Tregs infiltrating inflamed tissues exhibit distinct phenotypes dependent on the specific tissue sites and can display significant heterogeneity and tissue residency. Whether diverse allergic inflammatory responses in the lung influences infiltrating Treg heterogeneity or Treg lung residency has not previously been explored. We employed an unbiased single-cell RNAseq approach to investigate lung-infiltrating Tregs in models of eosinophilic and neutrophilic airway inflammation models, in which Tregs are critical regulators of inflammation. We found that lung-infiltrating Tregs are highly heterogeneous and that Tregs displaying lung resident phenotypes are significantly different depending on the types of inflammation. Tregs expression of ST2, a receptor for alarmin cytokine IL-33, was predominantly induced by eosinophilic inflammation and by tissue residency. However, Treg-specific ST2 deficiency did not affect the development of eosinophilic allergic inflammation nor the generation of lung resident Tregs. These results uncover a striking heterogeneity among Tregs infiltrating the lungs during allergic airway inflammation. The results also indicate that varying types of inflammation may give rise to phenotypically distinct lung resident Tregs, underscoring a novel mechanism by which inflammatory cues may shape the composition of infiltrating Tregs, allowing them to regulate inflammatory responses through tissue-adapted mechanisms.

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“…Due to the fatal systemic consequences with autoimmune events and multi-organ immune invasion and destruction upon mutation or deletion of Foxp3 , Treg cells are usually described as “guardians of peripheral immune tolerance”. In recent years, however, it has become evident that Treg cells can also be found in non-lymphoid tissues (NLTs), where they perform important homeostatic and regenerative functions ( 15 , 16 ). One prime example of a non-classical function of tissue Treg cells is from the visceral adipose tissue (VAT): In the murine system, local and systemic metabolic homeostasis has been linked to the presence and proper function of VAT-resident Treg cells, dependent on the interleukin (IL)-33 - ST2 axis, and tissue Treg cells expressing ST2 have also been found in the human system ( 17 – 19 ).…”

Section: Treg Cells Prevent Autoimmunity and Promote Tissue Regenerationmentioning

confidence: 99%

Stepwise acquisition of unique epigenetic signatures during differentiation of tissue Treg cells

et al. 2022

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Regulatory T cells in non-lymphoid tissues are not only critical for maintaining self-tolerance, but are also important for promoting organ homeostasis and tissue repair. It is proposed that the generation of tissue Treg cells is a stepwise, multi-site process, accompanied by extensive epigenome remodeling, finally leading to the acquisition of unique tissue-specific epigenetic signatures. This process is initiated in the thymus, where Treg cells acquire core phenotypic and functional properties, followed by a priming step in secondary lymphoid organs that permits Treg cells to exit the lymphoid organs and seed into non-lymphoid tissues. There, a final specialization process takes place in response to unique microenvironmental cues in the respective tissue. In this review, we will summarize recent findings on this multi-site tissue Treg cell differentiation and highlight the importance of epigenetic remodeling during these stepwise events.

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Implications of regulatory T cells in non-lymphoid tissue physiology and pathophysiology

Cited by 9 publications

References 212 publications

Alterations in peripheral T‐ and B‐cell subsets in patients with systemic sclerosis

Alterations in peripheral T‐ and B‐cell subsets in patients with systemic sclerosis

Single cell analysis uncovers striking cellular heterogeneity of lung infiltrating Tregs during eosinophilic vs. neutrophilic allergic airway inflammation

Stepwise acquisition of unique epigenetic signatures during differentiation of tissue Treg cells

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