Adipose tissue-derived mesenchymal stem cells induce expansion of interleukin-10-producing regulatory B cells and ameliorate autoimmunity in a murine model of systemic lupus erythematosus.
Taken together, this study demonstrates the key function of the hypoxia-associated transcription factor HIF-1α in driving IL-10 expression in CD1d<sup>hi</sup>CD5<sup>+</sup> B cells, and in controlling their protective activity in autoimmune disease.
On the other hand, the severity of the autoimmune diseases has been proven to be greater in the presence of high blood levels of IL-17, TNF-alpha, IL-6, IL-1-beta, IFN-gamma, and IL-18, in association with low levels of TGF-beta and IL-10.
Evidence supports that regulatory B cells (Bregs) produce negative regulatory cytokines, such as IL-10, which can negatively regulate immune responses in inflammation and autoimmune diseases.
Phagocyte-derived immunoregulatory cytokines such as Interleukin-12 and Interleukin-10 play pivotal roles in the etiology and pathology of many autoimmune diseases.
Our results suggest that IL-10 and IL-13 contribute to the pathogenesis of PSS and might explain the B cell abnormalities and the development of lymphoma observed in this autoimmune disease.
Here, we review the molecular mechanisms controlling IL-10 expression in B cells, and the evidence that IL-10-producing B cells play a protective role in human autoimmune diseases, underlying the relevance of this immunosuppressive axis for therapy.
Although IL-10 has been implicated in the pathogenesis of several autoimmune diseases, the mechanisms by which this cytokine mediates inflammatory lesions remain to be elucidated.
Recent studies have shown elevated IL-10 levels in several rheumatic autoimmune diseases, and particularly in systemic lupus erythematosus (SLE).Such changes may have a genetic basis.
Moreover, the ex vivo provision of CD40 and IL-21 receptor signals can drive B10-cell development and expansion by four-million-fold, and generate B10 effector cells producing IL-10 that markedly inhibit disease symptoms when transferred into mice with established autoimmune disease.
However, TGF-β and IL-10 also have pleiotropic effects and induce humoral immune responses depending on conditions, and thus their therapeutic application to autoimmune diseases remains limited.
Several studies attempted to investigate the role of various flavonoids mainly in experimental models of autoimmune diseases, especially in the context of their potential effect on the increase of regulatory T cells (Tregs) and their ability to stimulate an overexpression of anti-inflammatory cytokines, in particular that of IL-10.
Associations have been reported between single nucleotide polymorphisms (SNPs) of IL-10 and the Ile50Val polymorphism of the IL-4 receptor gene (IL-4R) gene and atopy and autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis.
These findings define a previously unrecognized signaling pathway that underlies IL-10 production by PGRN in T<sub>reg</sub> cells and present new insights into the mechanisms by which PGRN resolves inflammation in inflammatory conditions and autoimmune diseases, particularly inflammatory arthritis.-Fu, W., Hu, W., Shi, L., Mundra, J. J. Xiao, G., Dustin, M. L., Liu, C. Foxo4- and Stat3-dependent IL-10 production by progranulin in regulatory T cells restrains inflammatory arthritis.
Job's (hyper IgE) syndrome or inflammatory bowel disease (IBD) have now established a clear-cut role for the IL-10/STAT3 axis in immune tolerance; further understanding of these processes could lead to novel therapeutic approaches for autoimmune diseases.
Taken together, by enhancing IL-10 production and suppressing Th17 cells, the SCFA pentanoate might be of therapeutic relevance for inflammatory and autoimmune diseases.
Taken together, SLV appears to be a Th1-polarized autoimmune disease, whereby IFN-γ expression is strongly associated with parallel increases in IL-10 and IL-21, particularly during early and active stages of SLV.