Hydrogen Sulfide Reduces Myeloid-Derived Suppressor Cell-Mediated Inflammatory Response in a Model of -Induced Colitis.

Chronic inflammation contributes to tumor initiation in colitis-associated colorectal cancer (CRC). Indeed, inflammatory bowel disease (IBD) patients show an increased risk of developing CRC. Cancer immune evasion is a major issue in CRC and preclinical and clinical evidence has defined a critical role for myeloid-derived suppressor cells (MDSCs) that contribute to tumor growth and progression by suppressing T-cells and modulating innate immune responses. MDSCs comprise a heterogeneous population of immature myeloid cells that can be distinct in two subtypes: CD11bLy6GLy6C with granulocytic phenotype (G-MDSCs) and CD11bLy6GLy6C with monocytic phenotype (M-MDSCs). Hydrogen sulfide (HS) is an endogenous gaseous signaling molecule that regulates various physiological and pathophysiological functions. In particular, several studies support its anti-inflammatory activity in experimental colitis and ulcer. However, the role of the HS pathway in innate immune-mediated IBD has not yet been elucidated. To better define a possible link between MDSCs and HS pathway in colitis-associated CRC development, we used an innate immune-mediated IBD model induced by infection with the bacterium (), closely resembling human IBD. Here, we demonstrated an involvement of MDSCs in colitis development. A significant time-dependent increase of both G-MDSCs and M-MDSCs was observed in the colon and in the spleen of -infected mice. Following, we observed that chronic oral administration of the HS donor DATS reduced colon inflammation by limiting the recruitment of G-MDSCs in the colon of -infected mice. Thus, we identify the metabolic pathway l-cysteine/HS as a possible new player in the immunosuppressive mechanism responsible for the MDSCs-promoted colitis-associated cancer development.