Adoptive M2 type Macrophages Cell therapy of T1D

Type 1 diabetes (T1D) accounts for over 90% of childhood or adolescent diabetes. There is no doubt that the incidence of diabetes has increased in recent years, perhaps reflecting changes in lifestyle with regard to diet and/or hygiene. One explanation for the increased incidence of T1D is the hygiene hypothesis, which suggests that low or null exposure to some antigens, promotes the development of autoreactive leukocytes that attack pancreatic β cells, initiating the disease. Processing and presentation of autoantigenes by presenting cells like macrophages lead to activation of T helper cells (CD4+ TH). As a result of this, type 1 macrophages (M1) and cytotoxic T cells (CD8+) are activated by TH cells which destruct the β cells and cause other related disorders. Previous studies suggested that partial pancreatic duct ligation (PDL) which causes pancreatic tissue damage is accompanied by infiltration of inflammatory cells like M1 macrophages. M1 cells initiate the responses against β cells and cause their apoptosis directly by T cell activation and indirectly by secreting the inflammatory cytokines such as IL-1β, IL-6, and TNF-α. In contrast, M2 type macrophages have indicated the anti-inflammatory function in T1D unlike to M1 cells. M2 cells down-regulate the effect of inflammatory cytokines by producing IL-10 and TGF-β. Moreover, presence of M2 cells suppresses the M1 cells, dendritic cells and autoreactive T cells with significant enhancement of Treg cells. M2 cells with possessing the Immunoregulatory properties prevent the β cells destruction and preserve their survival. The other protective effects of M2 cells are including, tissue repairing, wound healing, improving diabetic nephropathy, and retinopathy. Based upon these findings, M2 cell or modified M2 cell can be a potential candidate for cell therapy of T1D.

Keywords:

Type 1 diabetes , Immune cell therapy , M2 macrophage , M1 macrophage , Pancreatic β cells