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Objectives We previously reported that ex vivo TGF-β and IL-2–induced CD8+CD103+ regulatory T cells (CD8+CD103+ iTregs) displayed similar immunosuppressive effect and therapeutic function on lupus mice nephritis to that of CD4+Foxp3+ Tregs. In view of the important role of glomerular endothelial cell (GEC) injury in inflammatory processes in SLE, this study aimed to investigate the nature and mechanism of CD8+CD103+ iTregs–mediated amelioration of LN by attenuating GEC injury. Methods Treg cells from patients with SLE and from healthy controls were characterized by flow cytometry analysis. The expression of pro-inflammatory mediators and VEGF were analysed in healthy controls, patients with SLE and MRL /lpr mice by ELISA, western blot, and real-time quantitative RT-PCR (qRT-PCR). Typical lesions of diffuse proliferative LN were observed in MRL /lpr mice through the use of haematoxylin and eosin, Masson, periodic acid–Schiff, periodic acid–Schiff methenamine, transmission electron microscopy and IF microscopy. Angiogenesis was analysed in GECs by cell investigating proliferation, migration, and tube formation. Results The results revealed that the frequency of Treg cells was inversely correlated with the expression of VCAM-1 and ICAM-1 in patients with SLE. Furthermore, adoptive transfer of CD8+CD103+ iTregs to MRL /lpr mice was associated with decreased levels of autoantibodies and proteinuria, reduced renal pathological lesions, and lowered renal deposition of IgG/C3. We further found that CD8+CD103+ iTregs not only suppressed the expression of pro-inflammatory mediators but also attenuated GEC injury by promoting angiogenesis. Conclusion Our study has identified the role of CD8+CD103+ iTregs on attenuating GEC injury and provided a possible application of this new iTregs subset in lupus nephritis and other autoimmune diseases. [ABSTRACT FROM AUTHOR]

During the entire processes of thymus organogenesis, maturation, and involution, gene regulation occurs post-transcriptionally via recently discovered microRNA (miRNA) transcripts. Numerous reports indicate that miRNAs may be involved in the construction of a normal thymic microenvironment, which constitutes a critical component to support T lymphocyte development. MiRNAs are also expressed in thymic stromal cells including thymic epithelial cells (TECs) during maturation and senescence. This review focuses on the function of miRNAs in thymic development and involution. A better understanding of these processes will provide new insights into the regulatory network of TECs and further comprehension of how genes control TECs to maintain the thymic microenvironment during thymus development and aging, thus supporting a normal cellular immune system. [ABSTRACT FROM AUTHOR]

Age-related thymic involution is primarily induced by defects in nonhematopoietic thymic epithelial cells (TECs). It is characterized by dysfunction of multiple transcription factors (TFs), such as p63 and FoxN1, and also involves other TEC-associated regulators, such as Aire. These TFs and regulators are controlled by complicated regulatory networks, in which microRNAs (miRNAs) act as a key player. miRNAs can either directly target the 3'-UTRs (untranslated regions) of the TFs to suppress TF expression or target TF inhibitors to reduce or increase TF inhibitor expression and thereby indirectly enhance or inhibit TF expression. Here, we review the current understanding and recent studies about how miRNAs are involved in age-related thymic involution via regulation of TEC-autonomous TFs. We also discuss potential strategies for targeting miRNAs to rejuvenate age-related declined thymic function. [ABSTRACT FROM AUTHOR]