Molecular mechanism for impaired suppressive function of Tregs in autoimmune diseases: A summary of cell‐intrinsic and cell‐extrinsic factors

Yang, Luting; Wang, Gang; Xia, Haibin

doi:10.1111/jcmm.15743

Cited by 11 publications

(8 citation statements)

References 55 publications

(64 reference statements)

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“…Immunosuppression mediated by regulatory T cells (Tregs) is not only one of the important mechanisms leading to the immune escape of tumor cells but also a key obstacle in tumor immunotherapy [15][16]. Tregs, a subset of CD4 + CD25 + FoxP3 + regulatory T cells with immunosuppressive functions, play an important role in maintaining immune tolerance and regulating the level of the immune response [17] and are positively correlated with the malignant progression of tumors. Clinical data show that pathogenic microorganisms in a variety of tumors can recruit Tregs [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Clinical Significance of Fusobacterium nucleatum Infection and Regulatory T Cell Enrichment in Esophageal Squamous Cell Carcinoma

Zhang

Liu

Yang

et al. 2021

Pathol. Oncol. Res.

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A variety of pathogenic microorganisms promote tumor occurrence and development through long-term colonization in the body. Fusobacterium nucleatum (F. nucleatum) is abundant in precancerous esophageal lesions and is closely related to the malignant progression of esophageal squamous cell carcinoma (ESCC). The invasion of exogenous microorganisms can reshape the immune microenvironment, make the immune system incapacitated, and assist tumor cells in immune escape. A variety of pathogenic microorganisms induce the recruitment of regulatory T cell (Tregs) to allow tumor cells to escape immune surveillance and provide favorable conditions for their own long-term colonization. Tregs are one of the major obstacles to tumor immunotherapy and have a significant positive correlation with the occurrence and development of many kinds of tumors. Because F. nucleatum can instantly enter cells and colonize for a long time, we speculated that F. nucleatum infection could facilitate the immune escape of tumor cells through enrichment of Tregs and promote the malignant progression of ESCC. In this study, we found a significant concordance between F. nucleatum infection and Tregs infiltration. Therefore, we propose the view that chronic infection of F. nucleatum may provide favorable conditions for long-term colonization of itself by recruiting Tregs and suppressing the immune response. At the same time, the massive enrichment of Treg may also weaken the immune response and assist in the long-term colonization of F. nucleatum. We analyzed the correlation between F. nucleatum infection with the clinicopathological characteristics and survival prognosis of the patients. F. nucleatum infection was found to be closely related to sex, smoking, drinking, degree of differentiation, depth of invasion, lymph node metastasis, and clinical stage. The degree of differentiation, depth of infiltration, lymph node metastasis, clinical stage, and F. nucleatum infection are independent risk factors affecting ESCC prognosis. Additionally, the survival rate and median survival time were significantly shortened in the F. nucleatum infection positive group. Therefore, we propose that long-term smoking and alcohol consumption cause poor oral and esophageal environments, thereby significantly increasing the risk of F. nucleatum infection. In turn, F. nucleatum infection and colonization may weaken the antitumor immune response through Treg enrichment and further assist in self-colonization, promoting the malignant progression of ESCC.

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Section: Introductionmentioning

confidence: 99%

Clinical Significance of Fusobacterium nucleatum Infection and Regulatory T Cell Enrichment in Esophageal Squamous Cell Carcinoma

Zhang

Liu

Yang

et al. 2021

Pathol. Oncol. Res.

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“…The locations of IBD are mainly happened in gut, a unique immune organ, and it would be damaged when the balance between pro-in ammatory cells and anti-in ammatory cells was destroyed [23,24]. Some pro-in ammatory cells such as Th1 and Th17, differentiated by naive T cells, exert in uence on inducing and maintaining intestinal in ammation by secreting effector cytokines, while Tregs, another kind of cells derived from Naive T cells, are important anti-in ammatory cells which suppress the function of pro-in ammatory cells [25][26][27]. Extensive evidence reveals that Tregs decrease in UC, and promoting the differentiation of Tregs alleviates the colitis of animal models [11,28,29].…”

Section: Discussionmentioning

confidence: 99%

BMSCs improve TNBS-induced colitis in rats through inducing Tregs differentiation by expressing PD-L1

Gao

Cui

Fan

et al. 2022

Preprint

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Objective: Bone marrow-derived mesenchymal stem cells (BMSCs) are a kind of stem cells with high differentiation potential and immunomodulatory ability, which has a broad prospect in the treatment of inflammatory bowel disease. The aim of this study is to investigate whether BMSCs could improve TNBS-induced colitis in Sprague-Dawley (SD) rats through inducing Tregs differentiation by expressing PD-L1.Methods: BMSCs were isolated and identified by flow cytometry before being transfected with PD-L1 siRNA recombinant plasmids. Then SD rats were randomly divided into 4 groups. Colitis induced by TNBS (sigma Aldrich) except normal group. On the fourth day of modeling, the rats in BMSCs control group and PD-L1 siRNA BMSCs group were injected with corresponding BMSCs through tail vein for 1 week, the dose was 5 × 106 cells. The normal group and model group were given the same volume of PBS.Results: PD-L1 siRNA BMSCs and BMSCs could reach colon tissue in TNBS-induced colitis. BMSCs control group significantly improved the clinical symptoms and histopathological severity of TNBS induced colitis, but PD-L1 siRNA BMSCs group did not. We found that the percentage of Tregs in spleen and mesenteric lymph nodes decreased, the expression of PD-L1, IL10, PTEN was down-regulated, and the expression of p-Akt and p-mTOR was up-regulated in colon tissue after PD-L1 siRNA intervention.Conclusion: This study suggested that BMSCs can induce the differentiation of Treg through inhibiting Akt/mTOR pathway by expressing PD-L1, which can significantly improve the symptoms and pathological damage of ulcerative colitis rats and affect the immune function.

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“…The MSCs from these tissues present the classic spindle shape and adhere to plastic. Additionally, MSCs can be isolated from different membranes of the placenta or different compartments of the umbilical cord individuals [43,44]. Previous study has demonstrated the reduction and dysfunction of Treg cells in SLE patients [45].…”

Section: Systemic Lupus Erythematosusmentioning

confidence: 99%

The therapeutic applications of mesenchymal stromal cells from human perinatal tissues in autoimmune diseases

Yang

You

et al. 2021

Stem Cell Res Ther

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The autoimmune diseases are characterized by overactivation of immune cells, chronic inflammation, and immune response to self-antigens, leading to the damage and dysfunction of multiple organs. Patients still do not receive desired clinical outcomes while suffer from various adverse effects imparted by current therapies. The therapeutic strategies based on mesenchymal stromal cell (MSC) transplantation have become the promising approach for the treatment of autoimmune diseases due to the immunomodulation property of MSCs. MSCs derived from perinatal tissues are collectively known as perinatal MSCs (PMSCs), which can be obtained via painless procedures from donors with lower risk of being contaminated by viruses than those MSCs from adult tissue sources. Therefore, PMSCs may be the ideal cell source for the treatment of autoimmune diseases. This article summarizes recent progress and possible mechanisms of PMSCs in treating autoimmune diseases in animal experiments and clinical studies. This review also presents existing challenges and proposes solutions, which may provide new hints on PMSC transplantation as a therapeutic strategy for the treatment of autoimmune diseases.

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Molecular mechanism for impaired suppressive function of Tregs in autoimmune diseases: A summary of cell‐intrinsic and cell‐extrinsic factors

Cited by 11 publications

References 55 publications

Clinical Significance of Fusobacterium nucleatum Infection and Regulatory T Cell Enrichment in Esophageal Squamous Cell Carcinoma

Clinical Significance of Fusobacterium nucleatum Infection and Regulatory T Cell Enrichment in Esophageal Squamous Cell Carcinoma

BMSCs improve TNBS-induced colitis in rats through inducing Tregs differentiation by expressing PD-L1

The therapeutic applications of mesenchymal stromal cells from human perinatal tissues in autoimmune diseases

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