The Role of Vitamin D and Omega-3 PUFAs in Islet Transplantation

Abstract

Recurrence of autoimmunity and allograft rejection represent major challenges that impact the success of islet transplantation. Despite the remarkable improvements achieved in immunosuppression strategies after the publication of the Edmonton protocol, long-term data of intra-hepatic islet transplantation show a gradual decline in beta-cell function. Therefore, there is a growing interest in the investigation of novel, safe and effective anti-inflammatory and immunomodulatory strategies able to promote long-term islet graft survival and notable improvements in clinical outcomes of islet transplant recipients. Vitamin D has been shown to exert anti-inflammatory and immunomodulatory effects. Pre-clinical studies investigating the use of vitamin D and its analogs (alone or in combination with immunosuppressive agents and/or other anti-inflammatory agents, such as omega-3 polyunsaturated fatty acids) showed beneficial results in terms of islet graft survival and prevention of recurrence of autoimmunity/allograft rejection in animal models of syngeneic and allogeneic islet transplantation. Moreover, epidemiologic studies demonstrated that vitamin D deficiency is highly prevalent after solid organ transplantation (e.g., heart, liver or kidney transplantation). However, studies that critically assess the prevalence of vitamin D deficiency among islet transplant recipients have yet to be conducted. In addition, prospective studies aimed to address the safety and efficacy of vitamin D supplementation as an adjuvant immunomodulatory strategy in islet transplant recipients are lacking and are therefore awaited in the future.

Common and personal target genes of the micronutrient vitamin D in primary immune cells from human peripheral blood

“…A 25(OH)D serum level below 50 nM may lead to musculoskeletal disorders, such as rickets in children and osteomalacia and fractures in adults 6 . Moreover, vitamin D insufficiency is linked to a large set of immunologic disorders, such as multiple sclerosis 7 , inflammatory bowel disease 8 , rheumatoid arthritis 9 , type I diabetes 10 , or infections like tuberculosis 11 as well as to cancers of colon, breast, prostate and blood 12 . Furthermore, individuals differ in their response to supplementation with vitamin D 3 , such as biochemical and physiological changes 13 , which led to the concept of the personal vitamin D response index 14 .…”

Combination of vitamin D and dipeptidyl peptidase-4 inhibitors (VIDPP-4i) as an immunomodulation therapy for autoimmune diabetes

“…Vitamin D deficiency is highly prevalent following solid organ transplantation [226]. Pre-clinical studies showed that vitamin D and its analogs have beneficial effects in terms of islet graft survival and prevention of allograft rejection and recurrence of autoimmunity in animal models of syngeneic and allogeneic islet transplantation [227]. Therefore, vitamin D supplementation has been suggested as a valid therapeutic strategy to reduce opportunistic infections and prevent allograft rejection after solid organ and cell transplantation [226,227].…”

“…Pre-clinical studies showed that vitamin D and its analogs have beneficial effects in terms of islet graft survival and prevention of allograft rejection and recurrence of autoimmunity in animal models of syngeneic and allogeneic islet transplantation [227]. Therefore, vitamin D supplementation has been suggested as a valid therapeutic strategy to reduce opportunistic infections and prevent allograft rejection after solid organ and cell transplantation [226,227]. In this regard, Zhou et al [228] found that vitamin D deficiency represents an independent risk factor for acute cellular rejection after liver transplantation.…”

Role of vitamin D in regulating COVID-19 severity—An immunological perspective

“…113,114 Anti-inflammatory effects of vitamin D are also implicated in successful organ transplantation. 73,[115][116][117][118] In endotoxin-induced acute respiratory distress syndrome (ARDS), inadequate vitamin D level is associated with increased levels of inflammatory cytokines such as IL-1 and TNF-. 119,120 In contrast to largely beneficial effects of vitamin D, certain infections (e.g., citrobacter and leishmania) were confusingly enhanced or unaffected by vitamin D. Subsequent categoric immunologic studies revealed inhibitory effects of vitamin D on inflammatory T H1 effector subset necessary for pathogen control.…”