We analysed the distribution of polymorphisms in the CTLA4, PTPN22, IL10, TNFalpha, FOXP3 and IRF5 genes that have been reported to be associated with a number of autoimmune disease.
These CD4(+)IFN-gamma(high)IL-4(low)IL-10(low)TGF-beta(low)FOXp3(-) cells in fact function as antigen-specific regulatory cells that restrain the development of autoimmunity by increasing the threshold of Th17 activation.
Recent studies demonstrated that the serum IL-10 and IL-18 levels may be influenced by genetics and related to susceptibility to several autoimmune diseases.
In support of a causal role for col(V) autoimmunity in the pathogenesis of atherosclerosis, col(V) sensitization of ApoE(-/-) mice on a regular chow diet overcame IL-10-mediated inhibition of col(V) autoimmunity, leading to increased atherosclerotic burden in these mice and local accumulation of IL-17-producing cells, particularly in the col(V)-rich adventitia subjacent to the atheromas.
Despite clear differences in clinical course and outcome, MFCPU and PIC may still represent two manifestations of the same disease, given their similar genetic associations with IL10 and TNF loci, which are known to be associated with noninfectious uveitis and autoimmunity, in general.
The capacities of transforming growth factor β (TGFβ) and IL10 to inhibit proinflammatory cytokine production by monocyte-derived dendritic cells (MoDC) or peripheral blood cells (PBMC) was analyzed in 75 children with IBD, including 13 infants with EO-IBD (in whom autoimmune diseases or classical immunodeficiencies were ruled out).
We conclude that the inheritance of a G allele at the interleukin-10-1082A/G polymorphism may favor a concurrent thyroid autoimmunity in differentiated thyroid carcinoma patients, and this autoimmunity may favor a better prognosis for these patients.
These data reveal a dominant immunosuppressive function of B-cell-derived IL-10 in the Lyn-deficient model of autoimmunity, extending our current understanding of the role of IL-10 and IL-10-producing B cells in systemic lupus erythematosus.
Using highly effective CD20 mAbs that efficiently deplete endogenous mature B cells and homologous CD20+ primary lymphoma cells through monocyte- and antibody-dependent mechanisms, we found that lymphoma depletion and survival were reduced when endogenous host B cells were not depleted, particularly a rare IL-10-producing B cell subset (B10 cells) known to regulate inflammation and autoimmunity.
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.
Three single nucleotide polymorphisms (SNPs), -1082, -819 and -592, located on the promoter region of IL10 gene have been associated with high in vitro IL-10 production and autoimmune diseases.
Dysregulation of IL-10 is associated with enhanced immunopathology in response to infection as well as increased risk for development of many autoimmune diseases.
Here, we discuss cellular source, gene regulation, and receptor complexes of cytokines in the IL10 cluster and their contribution to autoimmune disease and tissue damage.
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.
IL-10 is elevated in the serum and tissues of patients with systemic lupus erythematosus (SLE), an autoimmune disorder characterized by autoantibody production, immune-complex formation, and altered cytokine expression.
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.
The cytokines IL-6 and IL-10 are produced by cells of the adaptive and innate arms of the immune system and they appear to play key roles in genetically diverse autoimmune diseases such as relapsing remitting multiple sclerosis (MS), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
This review highlights the current knowledge on regulatory B cells, mainly IL-10-producing regulatory B cells, in animal models of inflammatory and autoimmune diseases and in clinical research using human samples.