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CD8+ regulatory T cells are critical in prevention of autoimmune-mediated diabetes

https://www.nature.com/articles/s41467-020-15857-x

https://www.ncbi.nlm.nih.gov/pubmed/32321922?dopt=Abstract

TITLE:
CD8+ regulatory T cells are critical in prevention of autoimmune-mediated diabetes.

DESCRIPTION:
Related Articles

CD8+ regulatory T cells are critical in prevention of autoimmune-mediated diabetes.

Nat Commun. 2020 04 22;11(1):1922

Authors: Shimokawa C, Kato T, Takeuchi T, Ohshima N, Furuki T, Ohtsu Y, Suzue K, Imai T, Obi S, Olia A, Izumi T, Sakurai M, Arakawa H, Ohno H, Hisaeda H

Abstract

Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing pancreatic β-cells are destroyed. Intestinal helminths can cause asymptomatic chronic and immunosuppressive infections and suppress disease in rodent models of T1D. However, the underlying regulatory mechanisms for this protection are unclear. Here, we report that CD8+ regulatory T (Treg) cells prevent the onset of streptozotocin -induced diabetes by a rodent intestinal nematode. Trehalose derived from nematodes affects the intestinal microbiota and increases the abundance of Ruminococcus spp., resulting in the induction of CD8+ Treg cells. Furthermore, trehalose has therapeutic effects on both streptozotocin-induced diabetes and in the NOD mouse model of T1D. In addition, compared with healthy volunteers, patients with T1D have fewer CD8+ Treg cells, and the abundance of intestinal Ruminococcus positively correlates with the number of CD8+ Treg cells in humans.

PMID: 32321922 [PubMed – indexed for MEDLINE]

PMID:
PubMed:32321922

DATE FOUND:
08/04/20 07:32AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32321922?dopt=Abstract

PD-1 and PD-L1 Expression in Peripheral CD4/CD8+ T Cells Is Restored in the Partial Remission Phase in Type 1 Diabetes

https://www.ncbi.nlm.nih.gov/pubmed/32236416?dopt=Abstract

TITLE:
PD-1 and PD-L1 Expression in Peripheral CD4/CD8+ T Cells Is Restored in the Partial Remission Phase in Type 1 Diabetes.

DESCRIPTION:
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PD-1 and PD-L1 Expression in Peripheral CD4/CD8+ T Cells Is Restored in the Partial Remission Phase in Type 1 Diabetes.

J Clin Endocrinol Metab. 2020 06 01;105(6):

Authors: Li X, Zhong T, Tang R, Wu C, Xie Y, Liu F, Zhou Z

Abstract

CONTEXT: Partial remission (PR) in type 1 diabetes (T1D) is accompanied by downregulation of the immune response. Programmed cell death-1 (PD-1) and its ligand (PD-L1) are important immunosuppressive molecules, but their changes in the PR phase are unclear.

OBJECTIVE: We investigated the dynamic changes of PD-1/PD-L1 expression on T cells around the PR phase in T1D.

METHODS: Ninety-eight T1D patients were recruited cross-sectionally and grouped according to PR status into nonremitters (individuals who did not undergo PR during the disease course; n = 39), pre-PR (n = 15), mid-PR (n = 30), and post-PR (n = 14) subgroups. PR was defined according to C-peptide level ≥300 pmol/L or index of insulin-adjusted hemoglobin A1c ≤9 as recommended. Among all the 98 patients, 29 newly diagnosed individuals were prospectively followed up for 1 year. The dynamic changes of PD-1/PD-L1 expression, frequency of regulatory T cells (Tregs) and IL-35+ Tregs among peripheral CD4/CD8+ T cells were determined.

RESULTS: PD-1/PD-L1 on CD4+/CD8+ T cells showed a dynamic change around the PR phase: lowest in pre-PR phase, restored in mid-PR phase, and declined again in post-PR phase. Conversely, this pattern did not occur for nonremitters. Notably, PD-1 expression on CD8+ T cells in mid-PR was positively correlated with the length of the PR phase. The percentages of circulating Tregs and IL-35+ Tregs showed no relation to PR.

CONCLUSIONS: The PR phase is associated with restoration of PD-1/PD-L1 on CD4+ and CD8+ T cells, suggesting that PD-1/PD-L1 may be a potential target for prolonging this phase in T1D.

PMID: 32236416 [PubMed – indexed for MEDLINE]

PMID:
PubMed:32236416

DATE FOUND:
01/30/21 06:12AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32236416?dopt=Abstract

Remission of autoimmune diabetes by anti-TCR combination therapies with anti-IL-17A or/and anti-IL-6 in the IDDM rat model of type 1 diabetes.

https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-1503-6

https://www.ncbi.nlm.nih.gov/pubmed/32106855?dopt=Abstract

TITLE:
Remission of autoimmune diabetes by anti-TCR combination therapies with anti-IL-17A or/and anti-IL-6 in the IDDM rat model of type 1 diabetes.

DESCRIPTION:
Related Articles

Remission of autoimmune diabetes by anti-TCR combination therapies with anti-IL-17A or/and anti-IL-6 in the IDDM rat model of type 1 diabetes.

BMC Med. 2020 Feb 28;18(1):33

Authors: Jörns A, Ishikawa D, Teraoku H, Yoshimoto T, Wedekind D, Lenzen S

Abstract

BACKGROUND: The cytokine IL-17 is a key player in autoimmune processes, while the cytokine IL-6 is responsible for the chronification of inflammation. However, their roles in type 1 diabetes development are still unknown.

METHODS: Therefore, therapies for 5 days with anti-IL-17A or anti-IL-6 in combination with a T cell-specific antibody, anti-TCR, or in a triple combination were initiated immediately after disease manifestation to reverse the diabetic metabolic state in the LEW.1AR1-iddm (IDDM) rat, a model of human type 1 diabetes.

RESULTS: Monotherapies with anti-IL-6 or anti-IL-17 showed no sustained anti-diabetic effects. Only the combination therapy of anti-TCR with anti-IL-6 or anti-IL-17 at starting blood glucose concentrations up to 12 mmol/l restored normoglycaemia. The triple antibody combination therapy was effective even up to very high initial blood glucose concentrations (17 mmol/l). The β cell mass was raised to values of around 6 mg corresponding to those of normoglycaemic controls. In parallel, the apoptosis rate of β cells was reduced and the proliferation rate increased as well as the islet immune cell infiltrate was strongly reduced in double and abolished in triple combination therapies.

CONCLUSIONS: The anti-TCR combination therapy with anti-IL-17 preferentially raised the β cell mass as a result of β cell proliferation while anti-IL-6 strongly reduced β cell apoptosis and the islet immune cell infiltrate with a modest increase of the β cell mass only. The triple combination therapy achieved both goals in a complimentary anti-autoimmune and anti-inflammatory action resulting in sustained normoglycaemia with normalized serum C-peptide concentrations.

PMID: 32106855 [PubMed – in process]

PMID:
PubMed:32106855

DATE FOUND:
02/29/20 06:34AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/32106855?dopt=Abstract

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