Type 1 Diabetic Children and Siblings Share a Decrease in Dendritic Cell and Monocyte Numbers but are Differentiated by Expansion of CD4+T Cells Expressing IL-17

Wilkinson, A; Bian, Lei; Khalil, Dalia; Gibbons, Kristen; Wong, Pooi-Fong; Hart, Derek N.J.; Harris, Mark; Cotterill, Andrew; Vučković, Slavica

doi:10.4172/2155-9899.s2-001

Cited by 7 publications

(9 citation statements)

References 42 publications

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“…We have shown the decrease of myeloid and plasmacytoid DC in T1D that is in keeping with previous studies [9,19]. Although our flow cytometry panel did not enable us to measure conventional DC (mDC) subtypes cDC1 and cDC2 [20], we characterized these cells by the expression of CD16 and slan, a carbohydrate modification of P-selectin glycoprotein ligand 1 (PSGL-1) that has been studied in the context of different immune-mediated diseases [12].…”

Section: Discussionsupporting

confidence: 82%

A study of 51 subtypes of peripheral blood immune cells in newly diagnosed young type 1 diabetes patients

Oras

Peet

Giese

et al. 2019

Clinical and Experimental Immunology

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Type 1 diabetes (T1D) results from autoimmune destruction of insulinproducing beta cells in pancreatic islets. Various immune cell populations are involved in disease development and natural course. However, to our knowledge, so far there are no comprehensive comparative investigations of all main immune cell populations and their most important subsets at the onset of disease. Therefore, in the current study, we analyzed 51 peripheral blood immune cell populations in 22 young T1D patients and in 25 age-matched controls using a comprehensive polychromatic flow cytometry panel developed for whole blood by the COST Action no. BM0907 ENTIRE (European Network for Translational Immunology Research and Education: From Immunomonitoring to Personalized Immunotherapy) consortium. We found that in T1D patients, frequencies and absolute counts of natural killer (NK) cells, dendritic cells (DC) and T cells, aswell as their respective subsets, were significantly altered compared to controls. Further, we observed that changes in several cell populations (e.g. CD14 + CD16 + non-classical monocytes, plasmablasts) were dependent on the age of the patient. In addition to age-related changes, we also found that alterations in immune cell patterns were associated with parameters such as the presence of ketoacidosis and C-peptide serum levels. Our study provides a foundation for future studies investigating different cell lineages and their role in T1D and illustrates the value of polychromatic flow cytometry for evaluating all main peripheral immune cells and their subsets in whole blood samples.

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Section: Discussionsupporting

confidence: 82%

A study of 51 subtypes of peripheral blood immune cells in newly diagnosed young type 1 diabetes patients

Oras

Peet

Giese

et al. 2019

Clinical and Experimental Immunology

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“…These comparisons likely missed critical genetic and environmental cues that underpin CD4 + Tm-cell pathomechanisms in T1D patients and siblings (33). In the current study, we identified several novel aspects of CD4 + Tm-cell biology common to T1D patients and siblings, including reduced absolute CD4 + Tm and CD4 + Tcm counts, exaggerated CD4 + Tem phenotype with an elevated IFN-g signature, heightened sensitivity to activation, and AICD.…”

Section: Discussionmentioning

confidence: 80%

Reactivated CD4+Tm Cells of T1D Patients and Siblings Display an Exaggerated Effector Phenotype With Heightened Sensitivity to Activation-Induced Cell Death

et al. 2014

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Dysfunction in effector memory has been proposed to contribute to autoimmunity in type 1 diabetes (T1D). Using a unique cohort of age- and sex-matched T1D patients, nonaffected siblings, and unrelated control children, we undertook a detailed analysis of proliferation, activation, effector responses, and apoptosis in reactivated CD4+Tm cells during T-cell receptor stimulation. Across cohorts, there was no difference in the proliferation of reactivated CD4+Tm cells. In T1D patients and siblings, CD4+Tm cells easily acquired the activated CD25+ phenotype and effectively transitioned from a central (CD62L+Tcm) to an effector memory (CD62L−Tem) phenotype with an elevated cytokine “signature” comprising interferon (IFN)-γ and interleukin-10 in T1D patients and IFN-γ in siblings. This amplified Tem phenotype also exhibited an exaggerated immune shutdown with heightened sensitivity to activation-induced cell death and Fas-independent apoptosis. Apoptosis resulted in the elimination of one-half of the effector memory in T1D patients and siblings compared with one-third of the effector memory in control subjects. These data suggest genetic/environment-driven immune alteration in T1D patients and siblings that manifests in an exaggerated CD4+Tem response and shutdown by apoptosis. Further immunological studies are required to understand how this exaggerated CD4+Tem response fits within the pathomechanisms of T1D and how the effector memory can be modulated for disease treatment and/or prevention.

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“…Some medications or drugs [29][30][31] used to treat hyperglycemia are associated with either an increased or reduced risk of cancer. Cancer and diabetes are diagnosed within the same individual more frequently than would be expected by chance, even after adjusting for age [32,33]. Both diseases are complex, with multiple subtypes.…”

Section: Liver Cancermentioning

confidence: 99%

A Confront on Cancer allied Diabetic Patients

R¹,

D²,

Nishanth³

2012

J Carcinogene Mutagene

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Insulin resistance, hyperinsulinemia and changes in signaling of different hormones associated with diabetes may affect the risk of breast cancer. We reviewed epidemiologic studies of the association between and risk of different types of cancers and the available evidence on the role of certain mediators of an association between diabetes and cancer. Many evidences supports the modest association between type 2 diabetes and the risk of cancer, the mechanisms underlying an association between diabetes and cancer risk remain unclear, particularly because the 2 diseases share several risk factors, including obesity, a sedentary lifestyle. Although the metabolic syndrome is closely related to diabetes and embraces additional components that might influence cancer risk.

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Type 1 Diabetic Children and Siblings Share a Decrease in Dendritic Cell and Monocyte Numbers but are Differentiated by Expansion of CD4+T Cells Expressing IL-17

Cited by 7 publications

References 42 publications

A study of 51 subtypes of peripheral blood immune cells in newly diagnosed young type 1 diabetes patients

A study of 51 subtypes of peripheral blood immune cells in newly diagnosed young type 1 diabetes patients

Reactivated CD4+Tm Cells of T1D Patients and Siblings Display an Exaggerated Effector Phenotype With Heightened Sensitivity to Activation-Induced Cell Death

A Confront on Cancer allied Diabetic Patients

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