Interleukin-35 administration counteracts established murine type 1 diabetes – possible involvement of regulatory T cells

Singh, K. N.; Kadesjö, Erik; Lindroos, Julia; Hjort, Marcus; Lundberg, Marcus; Espes, Daniel; Carlsson, Per‐Ola; Sandler, Stellan; Thorvaldson, Lina

doi:10.1038/srep12633

Cited by 52 publications

(78 citation statements)

References 58 publications

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“…MLDSTZ‐treated mice had increased blood glucose starting at day 7 and developed hyperglycemia gradually from day 10 while vehicle‐treated mice remained normoglycemic during the whole period of the study (Figure ). These data are consistent with our previous studies …”

Section: Resultssupporting

confidence: 94%

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Kinetics of immune cell responses in the multiple low‐dose streptozotocin mouse model of type 1 diabetes

et al. 2019

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In type 1 diabetes (T1D), the insulin‐producing β cells are destructed by immune mechanisms. It has been hypothesized that the very first immune response in T1D onset comes from innate immune cells, which further activates the adaptive immune cells to attack the islets. Despite intensive research on characterization of islet‐infiltrating immune cells, the kinetics of different immune cells in multiple low‐dose streptozotocin (MLDSTZ)‐induced T1D mouse model is still much unclear. Therefore, we investigated the proportions of innate immune cells such as neutrophils, dendritic cells (DCs), plasmacytoid dendritic cells (pDCs), macrophages, natural killer (NK) cells, and adaptive immune cells (T and B lymphocytes) in thymi, pancreatic‐draining lymph nodes, and spleens of MLDSTZ mice on days 3, 7, 10, and 21 after the first injection of STZ by flow cytometry. The proportions of DCs and B cells were increased from day 3, while the proportions of B‐1a lymphocytes and interferon‐γ+ cells among NK cells were increased, but NK cells were decreased on day 10 in MLDSTZ‐treated mice, illustrating that the initial immune response is induced by DCs and B cells. Later, the proportions of T helper 1 and cytotoxic T cells were increased from day 7, suggesting that the innate immune cells precede adaptive immune cell response in MLDSTZ mice. Altogether, our data demonstrate a possible sequence of events regarding the involvement of DCs, pDCs, NK cells, B‐1a lymphocytes, B, and T cells at the early stage of T1D development.

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Section: Resultssupporting

confidence: 94%

“…Single cell suspensions from thymic glands, PDLNs, and spleens were prepared as described earlier . Briefly; the thymic glands and spleens were mechanically disrupted in HBSS with a pair of forceps.…”

Section: Methodsmentioning

confidence: 99%

Kinetics of immune cell responses in the multiple low‐dose streptozotocin mouse model of type 1 diabetes

et al. 2019

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“…6d; Supplementary Fig. S7), suggesting a phenotypic shift of the Treg cells under inflammatory conditions, as observed earlier in a mouse model of type I diabetes32 and in RA3334.…”

Section: Resultssupporting

confidence: 78%

Overexpression of heparanase enhances T lymphocyte activities and intensifies the inflammatory response in a model of murine rheumatoid arthritis

Digre

Singh

Åbrink

et al. 2017

Sci Rep

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Heparanase is an endo-glucuronidase that degrades heparan sulfate chains. The enzyme is expressed at a low level in normal organs; however, elevated expression of heparanase has been detected in several inflammatory conditions, e.g. in the synovial joints of rheumatoid arthritis (RA) patients. Herein, we have applied the model of collagen-induced arthritis (CIA) to transgenic mice overexpressing human heparanase (Hpa-tg) along with wildtype (WT) mice. About 50% of the induced animals developed clinical symptoms, i.e. swelling of joints, and there were no differences between the Hpa-tg and WT mice in the incidence of disease. However, Hpa-tg mice displayed an earlier response and developed more severe symptoms. Examination of cells from thymus, spleen and lymph nodes revealed increased innate and adaptive immune responses of the Hpa-tg mice, reflected by increased proportions of macrophages, antigen presenting cells and plasmacytoid dendritic cells as well as Helios-positive CD4+ and CD8+ T cells. Furthermore, splenic lymphocytes from Hpa-tg mice showed higher proliferation activity. Our results suggest that elevated expression of heparanase augmented both the innate and adaptive immune system and propagated inflammatory reactions in the murine RA model.

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“…lymphocytes play a crucial role in controlling the immune responses; these immune cells produce several cytokines [19]. A recent study has reported that IL-35 is produced by regulatory T cells to suppress autoimmune and inflammatory responses, in other words, to counteract the autoimmune attack [20]. Taken together, these explanations give a good support to the highly significant increase in IL-35 level in CKF patients compared with healthy control ( table 1) .…”

Section: Introductionsupporting

confidence: 73%

Determination of IL-35, PTH, Ferritin and Other biochemical. Parameters in sera of Iraqi Men with chronic kidney failure

Zuhair¹,

Muajed²

2017

DJPS

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Chronic kidney Failure, a progressive disease, includes both medical and biochemical features that damage kidneys and decrease their abilities to work effectively, this disease is characterized by a chronic disorders to both the innate and adaptive immune systems, generate a complex and not fully understood immune dysfunction. In the present study, (30) men suffering from chronic kidney failure with age in range (40-55) year and (30) healthy men within the same range of age were enrolled in this study. The aim of this study is to highlight the role of immunological aspect (IL-35), hormonal aspects (PTH), some functional proteins and immunological electrolytes in sera of chronic kidney failure (CKF) patients.Biochemical parameters were determined in the sera of both patients and (healthy) control group. Patients enrolled in this study were newly diagnosed, they have not taken any treatment related to any chronic disease. Blood samples were collected and biochemical parameters were measured in Al-Karama teaching hospital in Baghdad (except IL-35 which was determined in the private Al-Ghazalia Laboratory) from April to November 2015. Results have reported that IL-35 level was highly significant increase in sera of chronic kidney failure patients (35.035± 0.025) pg/mL compared with healthy group (23.331±0.031) pg/mL. As well, PTH level was highly significant increased in patients group (235.032±3.841) pg/ml compared with healthy control group (49.96±0.308) pg/mL. Hemoglobin level was highly significant decreased ( 9.696±0.056) g/L in patients with control group (15.332±0.067) g/dL.

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Interleukin-35 administration counteracts established murine type 1 diabetes – possible involvement of regulatory T cells

Cited by 52 publications

References 58 publications

Kinetics of immune cell responses in the multiple low‐dose streptozotocin mouse model of type 1 diabetes

Kinetics of immune cell responses in the multiple low‐dose streptozotocin mouse model of type 1 diabetes

Overexpression of heparanase enhances T lymphocyte activities and intensifies the inflammatory response in a model of murine rheumatoid arthritis

Determination of IL-35, PTH, Ferritin and Other biochemical. Parameters in sera of Iraqi Men with chronic kidney failure

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