Alterations of peripheral CD4+CD25+Foxp3+ T regulatory cells in mice with STZ-induced diabetes

Yu, Zhen; Sun, Lina; Liu, He; Duan, Kaizhong; Zeng, Chun; Zhang, Lianjun; Jin, Dong-Yan; Peng, Jiao; Ding, Wenjun; Zhao, Yong

doi:10.1038/cmi.2011.37

Cited by 33 publications

(21 citation statements)

References 45 publications

(29 reference statements)

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“…To further assess whether indirubin alters the suppressive function of CD4 + CD25 + Foxp3 + Treg cells in ITP mice, we thus compared the immunosuppressive effects of CD4 + CD25 + Treg cells sorted by bead separation from ITP mice treated with or without indirubin using an in vitro immunosuppressive assay [ 18 ]. Naive CD4 + CD25 - T cells were used as responder cells as described in the materials and methods.…”

Section: Resultsmentioning

confidence: 99%

Indirubin Increases CD4+CD25+Foxp3+ Regulatory T Cells to Prevent Immune Thrombocytopenia in Mice

et al. 2015

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Indirubin, a traditional Chinese medicine, is used to treat autoimmune diseases in clinics. However, the effects of indirubin on the immunosuppressive CD4+CD25+Foxp3+ regulatory T cells (Treg) have not been addressed. Thus, we aimed to investigate the effects of indirubin on CD4+CD25+Treg cells in immune thrombocytopenia (ITP) CBA mice, which were established by immunization with Wistar rat platelets. 50 mg/kg indirubin treatment daily for 4 weeks significantly decreased anti-platelet antibody production and prevented the decrease of platelets caused by immunization in ITP mice. Consistently, indirubin significantly enhanced the percentage and cell number of CD4+CD25+Foxp3+Treg cells in the peripheral blood, spleen and lymph nodes. We also observed a significant increase of the frequency and cell number of CD4+CD25+Foxp3+Treg cells in the thymus upon indirubin treatment. Furthermore, CD4+CD25+Treg cells from indirubin-treated mice showed similar immunosuppression on T effector cells as compared to those from control mice. Altogether, indirubin ameliorates ITP by enhancing CD4+CD25+Foxp3+Treg cell level with preserving immunosuppressive function.

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Section: Resultsmentioning

confidence: 99%

Indirubin Increases CD4+CD25+Foxp3+ Regulatory T Cells to Prevent Immune Thrombocytopenia in Mice

et al. 2015

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“…Tregs are essential for the regulation of excessive inflammatory responses in the body, but the population size and function of Tregs in hyperglycemia-induced inflammation is controversial. Some researchers have shown that the frequencies and functions of Tregs do not change or decrease in hyperglycemic NOD mice 27 28 , whereas STZ-induced hyperglycemia in mice leads to an increased Treg population from the thymus and enhanced generation of Tregs in the periphery 29 . In accordance with this previous report related to STZ-induced hyperglycemia, we showed that Tregs were significantly increased in the inflamed liver tissues and mesenteric lymph nodes from the diabetic mice.…”

Section: Discussionmentioning

confidence: 99%

Hepatic immunophenotyping for streptozotocin-induced hyperglycemia in mice

Lee

Eun

Kim

et al. 2016

Sci Rep

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Emerging evidence revealed that diabetes induces abnormal immune responses that result in serious complications in organs. However, the effect of hyperglycemia on hepatic immunity remains obscure. We evaluated the population and function of hepatic immune cells in streptozotocin (STZ)-induced hyperglycemic mice. CC chemokine receptor 2 (CCR2)-knockout mice and mice with a depletion of regulatory T cells (DEREG) were used to investigate the migration and role of regulatory T cells (Tregs) in hyperglycemic mice. The inflammatory cytokines and hepatic transaminase levels were significantly increased in the hyperglycemic mice. The population and number of infiltrating monocytes, granulocytes, and Tregs were enhanced in the livers of the hyperglycemic mice. Hepatic monocytes other than macrophages showed the increased expression of inflammatory cytokines and chemokines in the hyperglycemic mice. The CCR2 knockout and DEREG chimeric mice exhibited increased populations of activated T cells and neutrophils compared to the WT chimeric mice, which promoted hepatic inflammation in the hyperglycemic mice. The migration of CCR2 knockout Tregs into the liver was significantly reduced compared to the WT Tregs. We demonstrated that hyperglycemia contributes to increase in infiltrating monocytes and Tregs, which are associated with hepatic immune dysfunction in mice. CCR2-mediated migration of Tregs regulates hyperglycemia-induced hepatic inflammation.

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“…The emergence of diabetogenic T cells appears to be associated with defective immunoregulation [5] . Numerical and functional deficiencies of CD4 + FoxP3 + T regulatory (Treg) cells have been demonstrated in T1D [6] , [7] . However, Treg cells do not account for the entire regulatory functions; another regulatory T cell subset, invariant natural killer T (iNKT) cells, has also been demonstrated to be involved in the pathophysiology of the disease.…”

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confidence: 99%

Regulatory role of natural killer T cells in diabetes

2015

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Type 1 and type 2 diabetes are growing public health problems. Despite having different pathophysiologies, both diseases are associated with defects in immune regulation. Invariant natural killer T (iNKT) cells are innate-like T cells that recognize glycolipids presented by CD1d. These cells not only play a key role in the defense against pathogens, but also exert potent immunoregulatory functions. The regulatory role of iNKT cells in the prevention of type 1 diabetes has been demonstrated in murine models and analyzed in diabetic patients. The decreased frequency of iNKT cells in non-obese diabetic mice initially suggested the regulatory role of this cell subset. Increasing the frequency or the activation of iNKT cells with agonists protects non-obese diabetic mice from the development of diabetes. Several mechanisms mediate iNKT regulatory functions. They can rapidly produce immunoregulatory cytokines, interleukin (IL)-4 and IL-10. They induce tolerogenic dendritic cells, thereby inducing the anergy of autoreactive anti-islet T cells and increasing the frequency of T regulatory cells (Treg cells). Synthetic agonists are able to activate iNKT cells and represent potential therapeutic treatment in order to prevent type 1 diabetes. Growing evidence points to a role of immune system in glucose intolerance and type 2 diabetes. iNKT cells are resident cells of adipose tissue and their local and systemic frequencies are reduced in obese patients, suggesting their involvement in local and systemic inflammation during obesity. With the discovery of potential continuity between type 1 and type 2 diabetes in some patients, the role of iNKT cells in these diseases deserves further investigation.

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Alterations of peripheral CD4+CD25+Foxp3+ T regulatory cells in mice with STZ-induced diabetes

Abstract: Complications arising from abnormal immune responses are the major causes of mortality and morbidity in diabetic patients.

Cited by 33 publications

References 45 publications

Indirubin Increases CD4+CD25+Foxp3+ Regulatory T Cells to Prevent Immune Thrombocytopenia in Mice

Indirubin Increases CD4+CD25+Foxp3+ Regulatory T Cells to Prevent Immune Thrombocytopenia in Mice

Hepatic immunophenotyping for streptozotocin-induced hyperglycemia in mice

Regulatory role of natural killer T cells in diabetes

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