## 3 Therapeutic Potential of Exosomes in Different Diseases
### Therapeutic Potential of Exosomes in Autoimmune Disease  
The beneficial roles of exosomes in immune tolerance and stimulation cannot be overemphasized as they are involved in several pathways such as angiogenesis, inflammation, and immune signaling. Exosomes have also acted as good tools for drug delivery due to their inherent biological features such as biocompatibility and stability including the capacity for permeation [110]. Sjogren's syndrome (SS) is an important autoimmune disorder characterized by lymphocytic infiltration in the salivary and lacrimal glands as well as the existence of numerous autoantibodies. These autoantibodies include anti-La (SS-B) or anti-Ro (SS-A)) with clinical syndromes such as ocular and oral dryness [111]. SS pathogenesis involves both innate and adaptive immune mechanisms such as NF-kB signaling, interferon (IFN) signatures, and B cell-activating factor (BAFF)/BAFF receptor axis [112]. Furthermore, salivary gland epithelial cells (SGECs) play an important role in both autoimmune and inflammatory responses in SS by inducible expression of different immunoreactive factors such as autoantiic ribonucleoproteins (RNPs), many Toll-like receptors (TLRs), and BAFF. Lymphocytic infiltration, mainly B and CD4\({}^{+}\) T cells, occurs and invades epithelial cells. This highlights the correlation between immune and epithelial cells [110]. A previous study documented the continuous release of autoantiic exosomes La/SS-B, Sm RNPs, and Ro/SS-A by SGECs, documenting the transfer of intracellular autoantigens to autoreactive lymphocytes within RNP-containing exosomes [60]. It was also observed that EBV-miRNABART13-3p in exosomes is transferrable from B cells to SGECs in EBV infected B cells. The stromal interacting molecule 1 (STIM1) and aquaporin 5 (AQP5) targeted by functional miRNA could significantly affect salivary secretion [12]. Recently, it was observed that subconjunctival administration of MSC-Exos to rabbits inhibited lacrimal gland inflammation in the affected group compared with the control group administered normal saline. It was concluded that MSC-Exo effects were partly due to the polarization of the lacrimal macrophage as well as the responses of Treg and Th2 by NF-kB signaling pathways. Thus, MSC-Exos may be useful in the treatment of dry eye [113]. Experimental autoimmune uveoreticinitis (EAU) could be effectively resolved by the use of bone marrow-derived MSC-Exos [114]. It was observed that in experimentally induced autoimmune uveitis in rats, human-derived Mesenchymal stem cell-derived exosomes inhibited the migration of inflammatory cells, mainly T cell subsets, in the eyes. Additionally, the MSC-Exo inhibited the chemo attractive effects of CCL2 and CCL21 on inflammatory cells [45]. Another experimental study conducted on EAU found that human umbilical cord-derived MSC-Exos (hUC-MSC-Exos) did not inhibit the progression of conA-stimulated T cells, but suppressed inflammatory cell migration [115]. The suppressive effect of hUC-MSC-Exos on the interphotoreceptor retinoid-binding protein (IRBP)-specific Th17 responses via the regulation of DC-derived Th17-polarizing cytokines IL-1\(\beta\), IL-6, and IL-23 led to the suppression of DC-driven Th17 responses [116]. Thus, it is clear that MSC-Exos can play a role in the treatment of auto-immune uveitis, however, further trials are essential to identify their immunomodulatory and anti-inflammatory effects [112].