Abstract
CD4+ T cells are one of the key immune cells contributing to the immunopathogenesis of type 1 diabetes (T1D). Previous studies have reported that platelet-derived mitochondria suppress the proliferation of peripheral blood mononuclear cells (PBMC). To further characterize the immune modulation of platelet-derived mitochondria, the purified CD4+ T cells were treated, respectively, with platelet-derived mitochondria. The data demonstrated that MitoTracker Deep Red-labeled platelet-derived mitochondria could directly target CD4+ T cells through C-X-C motif chemokine receptor 4 (CXCR4) and its ligand stromal cell-derived factor-1 (SDF-1), regulating the anti-CD3/CD28 bead-activated CD4+ T cells. The result was an up-regulation of Naïve and central memory (TCM) CD4+ T cells, the down-regulation of effector memory (TEM) CD4+ T cells, and modulations of cytokine productions and gene expressions. Thus, platelet-derived mitochondria have a translational potential as novel immune modulators to treat T1D and other autoimmune diseases.
Highlights
Type 1 diabetes (T1D) is one of the most common autoimmune diseases which is characterized by the destruction of insulin-producing β cells by autoreactive T cells
The current study demonstrated that platelet-derived mitochondria act as novel immune modulators on the anti-CD3/CD28 bead-activated CD4+ T cells, which exhibited multiple changes including cell surface markers, functionality, cytokine productions, and gene expressions after mitochondrial treatment
Based on the co-localization of MitoTracker Deep Red-positive platelet-derived mitochondria and MitoTracker Green-positive intrinsic mitochondria in CD4+ T cells, together with the significant up-regulation of mitochondrial DNA (mtDNA)-specific gene markers ND1 and ND5 in CD4+ T cells, these data suggest that platelet-derived mitochondria may enter into CD4+ T cells
Summary
Type 1 diabetes (T1D) is one of the most common autoimmune diseases which is characterized by the destruction of insulin-producing β cells by autoreactive T cells. Due to the lack of CCR7 expression, CD4 TEM cannot return to lymph/blood circulation and become the resident memory cells remaining in tissues [3,4,6,7]. These resident autoimmune memory CD4 TEM cells may replicate quickly and evoke the immune system to destroy the newly-generated islet β cells. These autoimmune memory T cells need to be eradicated in order to fundamentally correct the autoimmunity of T1D. It will be essential to modulate CD4+ T cells for the treatment of other autoimmune disease such as multiple sclerosis (MS) [8] and infection diseases [9], due to their dominant roles in orchestrate the innate and adaptive immune responses
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