IL-15 is elevated in serum patients with type 1 diabetes mellitus

Kuczyński, Sebastian; Winiarska, Hanna; Abramczyk, Małgorzata; Szczawińska, K; Wierusz‐Wysocka, Bogna; Dworacka, Marzena

doi:10.1016/j.diabres.2005.02.007

Cited by 55 publications

(38 citation statements)

References 25 publications

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“…Interestingly, it was previously suggested that individuals with type 1 diabetes exhibit a deficient production of interleukin-2, a potent NK cell stimulator (35,36). On the other hand, serum levels of interleukin-15 and -12, other molecules implicated in NK cell physiology, were found to be elevated in patients with type 1 diabetes (37,38). Another potential explanation would be an alteration in the systemic level of ligands that engage activating receptors on NK cells, reducing their expression.…”

Section: Discussionmentioning

confidence: 99%

Altered Natural Killer Cells in Type 1 Diabetic Patients

et al. 2007

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Evidence from animal models suggests that natural killer (NK) cells can be important players in the development of type 1 diabetes, although data in humans are still sparse. We studied the frequency and activation state of blood NK cells at different stages of human type 1 diabetes, and whether genetic or phenotypic NK cell peculiarities could be associated with an early onset of diabetes. The onset period is marked by a slight reduction in blood NK cells, but these are unusually activated in some patients (␥-interferon expression). This activation status does not correlate, however, with a particularly young age at onset. In contrast, NK cells in patients with long-standing type 1 diabetes had a markedly lower expression of p30/p46 NKactivating receptor molecules compared with those of control subjects. A slightly decreased expression of NKG2D in all type 1 diabetic patients relative to control subjects was observed, independent of the duration of disease, parallel to prior observations in the NOD mouse. Finally, type 1 diabetic patients had an increased frequency of KIR gene haplotypes that include the activating KIR2DS3 gene, with a genetic interaction between the KIR and HLA complexes. The reduced activation of NK cells in individuals with long-standing type 1 diabetes would seem to be a consequence rather than a cause, but other peculiarities may relate to type 1 diabetes pathogenesis. Diabetes 56: 177-185, 2007

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Section: Discussionmentioning

confidence: 99%

Altered Natural Killer Cells in Type 1 Diabetic Patients

et al. 2007

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“…Reports have indicated an association of increased levels of IL-15 with autoimmune diseases. Elevated serum IL-15 levels have been described in patients with chronic progressive multiple sclerosis, 52 type I diabetes, 53 and systemic lupus erythematosus. 54 Elevated local amounts of IL-15 have also been observed at sites of inflammation, 55,56 including the synovium in rheumatoid arthritis, 57,58 and anti-IL-15 therapy is effective in rheumatoid arthritis patients.…”

Section: Discussionmentioning

confidence: 99%

IL-15 maintains T-cell survival via S-nitrosylation-mediated inhibition of caspase-3

et al. 2014

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Caspase activity is critical for both T-cell survival and death. However, little is known regarding what determines caspase activity in cycling T cells. Interleukin (IL)-2 and IL-15 confer very different susceptibilities to T-cell death. We therefore considered that IL-2 and IL-15 differentially regulate caspase activity to influence T-cell survival. We observed that IL-2-cultured primary murine effector T cells manifested elevated levels of caspase-3 activity compared with IL-15-cultured T cells. T cell receptor (TCR) restimulation further increased caspase activity and induced considerable cell death in IL-2-cultured T cells, but provoked only a minimal increase of caspase activity and cell death in IL-15-cultured T cells. IL-2 sensitization to cell death was caspase-3 mediated. Interestingly, increased active caspase-3 levels with IL-2 were independent of active initiator caspase-8 and caspase-9 that were similar with IL-2 and IL-15. Rather, caspase-3 activity was inhibited by posttranslational S-nitrosylation in IL-15-cultured T cells, but not in the presence of IL-2. This paralleled increased reactive nitrogen and oxygen species with IL-15 and reduced glycolysis. Taken together, these data suggest that the metabolic state conferred by IL-15 inhibits T-cell apoptosis in part by maintaining low levels of active caspase-3 via S-nitrosylation.

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“…[14][15][16][17][18][19][20] For example, IL-15 has been proposed to be a required element in the pathogenesis of rheumatoid arthritis, inflammatory bowel disease, psoriasis, multiple sclerosis, type 1 diabetes, and refractory celiac disease, [14][15][16][17][18][19] as well as diseases associated with infection with the retrovirus HTLV-1 Figure 6. PBMCs from patients with T-LGL leukemia do not manifest ex vivo spontaneous proliferation in a 6-day ex vivo culture.…”

Section: Discussionmentioning

confidence: 99%

“…18,19,[45][46][47][48] In such patients, gluten peptides are presented by APCs to cognate gluten-specific CD4 ϩ T-lymphocytes. Furthermore, extensive intraepithelial infiltration of CD8 ϩ T-lymphocytes is a hallmark.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11][12] Interference with self-tolerance mediated by IL-2-induced activation-induced cell death and regulatory T cells and the facilitation of the maintenance of CD8 ϩ memory T-cell survival that include self-reactive memory T cells suggests that disordered IL-15 expression might contribute to the development of autoimmune disease. 13 Indeed, dysregulated IL-15 expression has been reported in patients with a range of autoimmune diseases including rheumatoid arthritis, 14 multiple sclerosis, 15 ulcerative colitis, 16 refractory celiac disease, [17][18] type 1 diabetes, 19 and diseases associated with the retrovirus HTLV-1. 20 To address such putative IL-15-mediated disorders, agents that inhibit IL-15 activity have been developed.…”

Section: Introductionmentioning

confidence: 99%

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