In our system, increased production of IL-10 in lymph nodes coincides with elevated mRNA levels of SOCS1 and decreased levels of IL6. It is also known that IL-6 in the presence of TGF-b drives ROR-ct expression in naive T cells to Th17 cells, while the absence of IL-6 induces FoxP3 expression and expansion of T regulatory cells. At the studied time points, no differences in the number of T regulatory cells or serum levels of IL-17 could be detected, suggesting that this mechanism is less likely. The frequency of B cells is decreased both locally in lymph nodes and systemically in spleen of LNT-IL-10 mice compared with controls. This effect might be attributed mainly to decreased IL-6 levels as the cytokine originally was identified as a B-cell differentiation factor and plays an important role in the development of antibody-producing plasma cells. Beside the fact that fewer B cells can lead to lower levels of anti-CII IgG antibodies, the beneficial effects of a reduced B cell population is well described in the outcome of human RA by the use of B cell depleting anti-CD20 antibodies. Our study suggests that inflammation-dependent IL-10 production causing locally increased levels of IL-10, increased SOCS1 mRNA and a decrease in systemic IL-6 levels ameliorate the outcome of CIA in mice. However, the concept needs to be tested in human RA, as the role of IL-10 in RA patients is far from clarified: RA patients have significantly elevated levels of IL-10 in synovial fluid while the expression of IL-10 receptors are reduced in synovial tissue compared with osteoarthritic controls, and treatment with systemic recombinant IL-10 in human RA patients has so far not shown any convincing results. Although these findings appear disappointing they do not contradict our data. Rather, they suggest that the anti-arthritogenic effect might be dependent on a requirement for localised rather than systemic IL-10 treatment. The involvement of ETS genes in cancer was first demonstrated by the presence of the oncogene v-ets as part of the gag-myb-ets transforming fusion protein of an avian retrovirus, E26. Their importance in human carcinogenesis is supported by the observations that ETS genes are implicated in chromosomal translocations, giving rise to fusion proteins that play an important role in the genesis of several hematological malignances, soft tissue tumors and carcinomas. The ETS family of transcription factors is one of the largest families of transcription regulators, and plays an important role in diverse MK-1775 biological processes, including cell proliferation, apoptosis, differentiation, lymphoid and myeloid cell development, angiogenesis and invasiveness. It is characterized by an 85 amino acidic, highly conserved, DNA binding domain, which displays sequence specific binding to purine-rich DNA sequences containing a 59-GGAA/T-39 core sequence. The Ewing’s sarcoma family of tumors serves as a paradigm for the entire class of ETS-related tumors, since more than 99% of the cases harbor translocations involving ETS genes and EWSR1. In 85% of the cases, the ESFT harbors a t chromosomal translocation, resulting in a fusion of the amino terminus of the EWSR1 gene to the carboxyl terminus of FLI1. Some of them may turn out to be more amenable to targeted therapy than the chimeric/truncated transcription factors themselves. Whereas several target genes relevant for ESFT have been uncovered, the search for the downstream effectors of aberrant ETS transcription factors in PCa is still in its infancy. The major ETS genes involved in rearrangements in ESFT and PCa, FLI1 and ERG, respectively, belong to the same subfamily.