Hemin Decreases Pro-Inflammatory Th17 Cells and Cytokines in an Adoptive Transfer Model of Colitis

Abstract

The goal of this research was to reduce disease in an adoptive transfer model of colitis using an immunomodulatory therapy, hemin, while correlating this response to changes in cytokines and effector T-cell differentiation. Inflammatory bowel disease (IBD) is a consequence of immune system dysregulation, mediated by the microbiomes composition (Gálvez, 2014). IBD is most prevalent and rising in developed parts of the world such as the United States where 1.5 million people and Europe where 2.2 million people are affected (Ananthakrishnan, 2015). Research for IBD in recent years has significantly advanced our knowledge of the complex pathways and interactions involved, however a complete and long lasting treatment remains unidentified. The rate-limiting enzyme HO-1 has been found to increase pools of regulatory T-cells (T-regs), while decreasing pools of pro-inflammatory Th17 cells in a chemically induced model of colitis. Here, the in-life phase which focused on body weight and video endoscopy support other primary outcomes from multiplex immunoassays and fluorescence activated cell sorting (FACS) from blood, colon, spleen, and mesenteric lymph node samples in an adoptive transfer model of colitis in mice. Pro-inflammatory cytokines IFN-γ and TNF-α and CD4+ T-cells in the blood at study conclusion were found to be significantly decreased in the hemin group, as were CD4+CD39+ T-cells in the blood from days 28-56. Further, in life data suggests a positive treatment effect showing a trend with higher body weights and lower endoscopy scores. Together these data demonstrate that hemin acts in an anti-inflammatory manner by modulating pathogenic T-cell proliferation and production of key pro-inflammatory cytokines.