Tolerogenic dendritic cells (tolDCs) are central players in the initiation and maintenance of immune tolerance and subsequent prevention of autoimmunity. Recent advances in treatment of autoimmune diseases including systemic lupus erythematosus (SLE) have focused on inducing specific tolerance to avoid long-term use of immunosuppressive drugs. Therefore, DC-targeted therapies to either suppress DC immunogenicity or to promote DC tolerogenicity are of high interest. This review describes details of the typical characteristics of in vivo and ex vivo tolDC, which will help to select a protocol that can generate tolDC with high functional quality for clinical treatment of autoimmune disease in individual patients. In addition, we discuss the recent studies uncovering metabolic pathways and their interrelation intertwined with DC tolerogenicity. This review also highlights the clinical implications of tolDC-based therapy for SLE treatment, examines the current clinical therapeutics in patients with SLE, which can generate tolDC in vivo, and further discusses on possibility and limitation on each strategy. This synthesis provides new perspectives on development of novel therapeutic approaches for SLE and other autoimmune diseases.
Opisthorchis viverrini causes public health problems in South-East Asia. Recently, TGF-β and IL-10 have been reported to increase in O. viverrini-infected hamsters but the sources of these cytokines are still unknown. In this study, the CD4 T cells in infected hamsters were investigated. It was demonstrated that IL-4 CD4 T cells were significantly increased in hamster spleens and mesenteric lymph nodes (MLNs) during chronic infection. Interestingly, IL-10 CD4 T cells were also discovered at a significant level while Treg (T regulatory)-like TGF- β CD4 T cells were in MLNs of infected hamsters. Moreover, the CD4 CD25 Foxp3 Treg cell response was significantly found both in spleens and MLNs in infected hamsters. The findings were then confirmed by development of T-cell clones against crude somatic antigens (CSAg) in immunized BALB/c mice. Five clones named TCC21, TCC23, TCC35, TCC41 and TCC108 were established. The TCC21 was found to be the TGF-β CD4 while TCC35, TCC41 and TCC108 were IL-4 CD4 and TCC23 was IFN-γ CD4 . This TGF-β CD4 T clone showed an inhibitory function in vitro in mononuclear cell proliferation via TGF-β-mediated mechanisms. This study indicated that O. viverrini-infected hamsters could induce TGF-β CD4 Treg-like cells. The CSAg-specific Tregs secreted high TGF-β, and limited immune cell proliferation.
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