Immune cell crosstalk in type 1 diabetes

Lehuen, Agnès; Diana, James S.; Zaccone, Paola; Cooke, Anne

doi:10.1038/nri2787

Cited by 406 publications

(417 citation statements)

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“…Converging studies in mouse models suggest that iNKT cells can prevent the development of type 1 diabetes [3]. iNKT cells are reduced in number in diabetes-prone NOD mice [4,5], and increasing the number of iNKT cells by adoptive transfer [6,7] or via the introduction of a Va14-Ja18 transgene, reduces significantly the progression of the disease [6].…”

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confidence: 99%

NOD mice contain an elevated frequency of iNKT17 cells that exacerbate diabetes

et al. 2011

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Invariant natural killer T (iNKT) cells are a distinct lineage of innate-like T lymphocytes and converging studies in mouse models have demonstrated the protective role of iNKT cells in the development of type 1 diabetes. Recently, a new subset of iNKT cells, producing high levels of the pro-inflammatory cytokine IL-17, has been identified (iNKT17 cells). Since this cytokine has been implicated in several autoimmune diseases, we have analyzed iNKT17 cell frequency, absolute number and phenotypes in the pancreas and lymphoid organs in non-obese diabetic (NOD) mice. The role of iNKT17 cells in the development of diabetes was investigated using transfer experiments. NOD mice exhibit a higher frequency and absolute number of iNKT17 cells in the lymphoid organs as compared with C57BL/6 mice. iNKT17 cells infiltrate the pancreas of NOD mice where they express IL-17 mRNA. Contrary to the protective role of CD4 1 iNKT cells, the CD4 À iNKT cell population, which contains iNKT17 cells, enhances the incidence of diabetes. Treatment with a blocking anti-IL-17 antibody prevents the exacerbation of the disease. This study reveals that different iNKT cell subsets play distinct roles in the regulation of type 1 diabetes and iNKT17 cells, which are abundant in NOD mice, exacerbate diabetes development.

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confidence: 99%

NOD mice contain an elevated frequency of iNKT17 cells that exacerbate diabetes

et al. 2011

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“…Extremely helpful in this regard have been animal models, notably the non-obese diabetic (NOD) mouse. This mouse and a host of important clinical research are bringing us closer to understanding immune cell crosstalk in T1DM [3]. This work has identified different immune cell types in pancreatic beta-cell destruction, including CD4+ and CD8+ T cells, macrophages, dendritic cells, natural killer cells, and the dendritic cell subtypes mentioned in this month's article [1].…”

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“…However, the greater role appears to be conducted by cellularly mediated immunity [3]. Extremely helpful in this regard have been animal models, notably the non-obese diabetic (NOD) mouse.…”

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“…Meyers et al have addressed this issue here [1]. Lehuen et al [3] indicated the TLR expression on pancreatic beta cells that would appear to be germane to the discussion. They pointed out that TLRs are expressed by pancreatic β-cells to detect danger from microbial products and can trigger T1DM.…”

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“…FASL-expressing T cells can mediate apoptosis through interaction with FAS expressed on β-cells. An abbreviated version of their illustration [3] is given (Fig. 1).…”

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From Toll-like receptors to the toll house of type 1 diabetes mellitus

Luft

2010

J Mol Med

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Impact of T cells on neurodegeneration in anti‐GAD65 limbic encephalitis

Dik

Widman

Schulte‐Mecklenbeck

et al. 2021

Ann Clin Transl Neurol

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Objective: Direct pathogenic effects of autoantibodies to the 65 kDa isoform of glutamic acid decarboxylase (GAD65) in autoimmune limbic encephalitis (LE) have been questioned due to its intracellular localization. We therefore hypothesized a pathogenic role for T cells. Methods: We assessed magnet resonance imaging, neuropsychological and peripheral blood, and CSF flow cytometry data of 10 patients with long-standing GAD65-LE compared to controls in a cross-sectional manner. These data were related to each other within the GAD65-LE group and linked to neuropathological findings in selective hippocampectomy specimen from another two patients. In addition, full-resolution human leukocyte antigen (HLA) genotyping of all patients was performed. Results: Compared to controls, no alteration in hippocampal volume but impaired memory function and elevated fractions of activated HLADR + CD4 + and CD8 + T cells in peripheral blood and cerebrospinal fluid were found. Intrathecal fractions of CD8 + T cells negatively correlated with hippocampal volume and memory function, whereas the opposite was true for CD4 + T cells. Consistently, antigen-experienced CD8 + T cells expressed increased levels of the cytotoxic effector molecule perforin in peripheral blood, and perforinexpressing CD8 + T cells were found attached mainly to small interneurons but also to large principal neurons together with wide-spread hippocampal neurodegeneration. 6/10 LE patients harbored the HLA-A*02:01 allele known to present the immunodominant GAD65 114-123 peptide in humans. Interpretation: Our data suggest a pathogenic effect of CD8 + T cells and a regulatory effect of CD4 + T cells in patients with long-standing GAD65-LE.

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Immune cell crosstalk in type 1 diabetes

Cited by 406 publications

References 138 publications

NOD mice contain an elevated frequency of iNKT17 cells that exacerbate diabetes

NOD mice contain an elevated frequency of iNKT17 cells that exacerbate diabetes

From Toll-like receptors to the toll house of type 1 diabetes mellitus

Impact of T cells on neurodegeneration in anti‐GAD65 limbic encephalitis

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