In particular, sirolimus dramatically suppressed oedema, reduced leucocyte infiltration and maintained mucosal integrity in TNBS-treated mice. These results apparently provide evidence of the therapeutic effect of sirolimus on experimental colitis and indicate that inhibition of the activity of mTOR is able to decrease the production of pro-inflammatory cytokines and disease parameters, thereby turning off the immune response learn more of TNBS-induced experimental colitis. In conclusion, the present study shows that pre-treatment with sirolimus, the inhibitor of

mTOR, alleviated the perpetuation of TNBS-induced colitis. This amelioration was paralleled by promoting differentiation of Treg cells and inhibiting the generation of Th17 cells. Sirolimus treatment resulted in a significant histological improvement, protecting against mucosal ulcerations. This study suggests that sirolimus-based pharmaceutical strategies may offer a promising alternative to our current approaches of managing IBD. The project was supported by Guangdong Natural Science Foundation

(Grant S2012010009409) and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry SAR245409 cell line [No (2011)1139]. The authors declare no conflict of interest. “
“We show that the T-cell immunoglobalin mucin, Tim-1, initially reported to be expressed on CD4+ T cells, is constitutively expressed on dendritic cells (DCs) and that its expression further increases after DC maturation. Tim-1 signaling into DCs upregulates costimulatory molecule expression and proinflammatory cytokine production, thereby promoting effector T-cell responses, while inhibiting Foxp3+ Treg responses. By contrast, Tim-1 signaling in T cells only regulates Th2 responses. Using a high-avidity/agonistic anti-Tim-1 antibody as a co-adjuvant enhances the immunogenic function of DCs, decreases the suppressive function of Tregs, and substantially increases proinflammatory Th17 responses in Quinapyramine vivo. The treatment with high- but not low-avidity anti-Tim-1 not only worsens experimental autoimmune encephalomyelitis

(EAE) in susceptible mice but also breaks tolerance and induces EAE in a genetically resistant strain of mice. These findings indicate that Tim-1 has an important role in regulating DC function and thus shifts the balance between effector and regulatory T cells towards an enhanced immune response. By understanding the mechanisms by which Tim-1 regulates DC and T-cell responses, we may clarify the potential utility of Tim-1 as a target of therapy against autoimmunity, cancer, and infectious diseases. The T-cell immunoglobulin mucin (Tim) family of proteins are expressed on various immune cells and regulate immune responses 1–3. Tim-1 was first identified as a hepatitis A virus cellular receptor 1 (HAVCR1) 4, 5 and later as a kidney injury molecule, KIM-1 6, 7.