Abstract
Type 1 diabetes (T1D) is prompted by defective immunological tolerance, an event in which dendritic cells (DCs) are crucial as immune response orchestrators. In fact, they contribute to maintaining tolerance to self-antigens, but they can also prompt an immunogenic response against them, leading to autoimmunity. Countless factors can potentially impact on the proper functionality of the DCs, which range from altered subset distribution, impaired phagocytic function to abnormal gene expression. Moreover, in T1D, metabolic dysregulation could impair DC functions as well. Indeed, since T1D clinical course is likely to be more aggressive in children and adolescents and entails severe dysglycemia, the aim of this study was to analyze circulating DCs subpopulations in pediatric T1D at different stages, as well as to characterize their phagocytosis ability and tolerance induction potential. Thus, pediatric patients newly diagnosed with T1D, with established disease and control subjects were recruited. Firstly, DCs subsets from peripheral blood were found quantitatively altered during the first year of disease, but recovered in the second year of progression. Secondly, to study the tolerogenic functionality of DCs, liposomes with phosphatidylserine (PS) were designed to mimic apoptotic beta cells, which are able to induce tolerance, as previously demonstrated by our group in DCs from adult patients with T1D. In this study, monocyte-derived DCs from pediatric patients with T1D and control subjects were assessed in terms of PS-liposomes capture kinetics, and transcriptional and phenotypic changes. DCs from pediatric patients with T1D were found to phagocyte PS-liposomes more slowly and less efficiently than DCs from control subjects, inversely correlating with disease evolution. Nonetheless, the transcription of PS receptors and immunoregulatory genes, cytokine profile, and membrane expression of immunological markers in DCs was consistent with tolerogenic potential after PS-liposomes phagocytosis. In conclusion, T1D progression in childhood entails altered peripheral blood DCs subsets, as well as impaired DCs phagocytosis, although tolerance induction could still function optimally. Therefore, this study provides useful data for patient follow-up and stratification in immunotherapy clinical trials.
Highlights
Type 1 diabetes (T1D) is prompted by defective immunological tolerance to beta cells, resulting in their destruction by autoreactive lymphocytes
dendritic cells (DCs) Subsets From Peripheral Blood Are Altered at the Onset and Early Stages of T1D Progression
The percentage of myeloid DCs (myDCs) was increased in patients at first year when compared to control subjects, patients at onset and at second year of progression, no differences were observed in their numbers
Summary
Type 1 diabetes (T1D) is prompted by defective immunological tolerance to beta cells, resulting in their destruction by autoreactive lymphocytes. The triggering factors causing their activation remain elusive, antigen-presenting cells (APCs) are known to contribute to this activation, and so, to the development of the disease. Among APCs, dendritic cells (DCs), as orchestrators of the immune response, play a crucial role in the process. Many factors could potentially impact on the proper functionality of the DCs, ranging from altered subset distribution, impaired phagocytic function, abnormal gene expression to defective functionality. As a case in point, many studies have linked the deficient removal of apoptotic beta cells performed by phagocytes to the initiation of autoimmunity [1]. Beta cells experience massive peaks of apoptosis, as a consequence of the autoimmune attack [2, 3], and in physiological islet remodeling during the perinatal period [4, 5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
