Inflammatory bowel disease (IBD) is a chronic condition characterized by continuous inflammation of the gastrointestinal tract that varies in intensity over time. IBD is caused by several factors including aberrant gut flora, immunological dysregulation, altered environmental conditions, and genetic variations. However, the pathogenesis of IBD remains unclear. Studies have indicated that an imbalance between T helper 17 (Th17) and regulatory T (Treg) cells contributes significantly to the development of IBD. Intestinal Tregs suppress inflammation and are critical for maintaining tissue homeostasis. Th17 cells are known to play an important role in the development and pathogenesis of IBD and provide non-inflammatory support for the integrity of the intestinal barrier against bacterial and fungal infections. Therefore, the Th17/Treg cell balance is crucial in the pathogenesis of IBD and gut integrity. The microenvironment of the intestinal mucosal immunity is regulated by the secretion of cytokines associated with Th17 cells and Tregs. Several studies have indicated that the gut bacteria contribute to the control of the immune milieu and play a key role in the regulation of Th17 cell development. Intestinal bacteria and cytokines control Th17 cell development. Th17 cells secrete cytokines that regulate the immune microenvironment in the gut mucosa. This review provides an overview of Th17 cells and examines the strategies for treating patients with IBD using Th17 cell-targeted drugs.

Serum amyloid A (SAA) is an acute phase protein with pro-inflammatory cytokine-like properties. Recent studies have revealed that SAA promotes γδT cell to produce IL-17 and T helper 17 (Th17) cells differentiation and function. In this study, we established the hepatic SAA1 overexpressed transgenic mice (TG). In this mouse, IL-17 was significantly increased in conditional state by γδT cell. We revealed that SAA1 mediated IL-17 producing from γδT cell is dependent on TLR2. Moreover we immunized SAA1 TG mice with Complete Freund’s adjuvant (CFA), which is well-known inducer of Th1 response and IFN-γ. We observed increased IL-17 secretion with increased Th17 cells and decreased IFN-γ, which is contrast to wild type mice (WT). In addition, we showed that locally increased transforming growth factor- β (TGF-β) followed by Th17 cells polarization might involve in Th17 cell maintenance by suppressing the expression of T-bet, a key transcription factor for the differentiation of T helper 1 (Th1) cells. These data demonstrate that SAA1 represent potent endogenous protein that drives IL-17 induced inflammation by γδT cell partially through TLR2 and by Th17 cell. Also these increased IL-17 response maintained by TGF-β Smad2/3 signaling. Therefore we could say that SAA is central player in IL-17 related inflammatory response.