Mice were treated with DSS to induce inflammation and given Anakinra throughout the second cycle of treatment. murine IL-10-/-DCs produced more IL-1 than their wild-type counterparts and promoted Th17 cell development in an IL-1-dependent manner. Finally,in vivoblockade of IL-1 receptor signaling reduced Th17 cell accumulation and inflammation in a mouse model of chemically-induced colitis. == Conclusions == Endogenous IL-10 constrains Th17 cell development through the control of IL-1 production by DCs, and reaffirms the crucial anti-inflammatory role of IL-10 in patients with chronic inflammation. Keywords:Th17, IL-10, IL-1, IL-17, inflammation, Crohn’s disease == Introduction == Inflammation is usually associated with autoimmune diseases and cancer development [1,2]. Recent studies have emphasized the relevance of Th17 cell function in human diseases, including multiple sclerosis [3], colitis [4,5], psoriasis [6,7] and malignancy [8,9]. It has been reported that a variety of cytokine cocktails including transforming growth factor beta (TGF) and the interleukins (IL)-6, IL-1, and IL-23 promote Th17 cell development [10-15], whereas IL-2 inhibits Th17 cell development [16]. It is generally accepted that these cytokines directly target T cells, where they regulate the expression of certain transcription factors and cytokine receptors, and impact Th17 cell development [17-19]. Importantly, however, effector T helper (Th) cells are polarized by antigen-presenting cells (APCs). The role of APC subsets including dendritic cells (DCs) and macrophages has not been studied in the development of Th17 cells in the microenvironment of intestinal mucosa in patients with Crohn’s disease (CD). In this study, we examined the effects of Crohn’s APCs and the associated cytokines on Th17 cell induction in patients with CD. We extended and confirmed our human studies in mouse model with chemically-induced IAXO-102 intestinal inflammation. Furthermore, we extended and confirmed our human studies in IL-10-deficient mouse model. IL-10-deficient mice show enhanced development of several DUSP5 inflammatory and autoimmune diseases [20], which partially micmics patients with CD. It suggests that IL-10 may serve a central function IAXO-102 in vivo in restricting inflammatory responses in patients with CD. In support of this possibility, it was recently reported that a CD-associated NOD2 mutation suppresses transcription of human IL-10 by inhibiting activity of the nuclear IAXO-102 IAXO-102 ribonucleoprotein hnRNP-A1, and low IL-10 expression is associated with this mutation [21]. IL-10 is an immunosuppressive cytokine that is produced by IAXO-102 several cell types, including myeloid APCs [22-25]. IL-10 often directly targets APCs in an autocrine manner and impedes T cell activation and polarization, thereby reducing inflammation [22,23,26-29]. Thus, it is possible that IL-10 affects the functionality of APCs, impacts Th17 cell development, and Th17-associated human pathogeneses. Thus, we assessed the role of APC-derived IL-10 in both patients with CD and IL-10-/-mouse model, and investigated the cellular and molecular relationship between IL-10 and Th17 cells in these two systems. Notably, there is strong genetic evidence that IL-23 plays a role in CD. IL-23 receptor polymorphisms were strongly associated with susceptibility to CD in genome-wide scans [30]. An elevation in transcripts encoding several inflammatory cytokines including IL-6, IL-8, IL-17, IL-23 and TNF is usually detected in intestinal biopsies from individuals with active CD [31]. On the basis of these results, clinical studies have begun with anti-IL-12p40 (IL-23p40) [32,33] or anti-IL-17 treatment in patients with autoimmune diseases including active CD [7]. Mixed clinical responses are reported in a variety of autoimmune diseases [7,32,33]. Our data demonstrate that endogenous IL-10, likely derived from DCs, constrains Th17 cell development through IL-1 in both scenarios. Our results and current clinical trials demonstrate that several key Th17-associated cytokines, rather than one specific cytokine (IL-17 or IL-23), play.