Hydrogen sulfide reduces myeloid-derived suppressor cell-mediated inflammatory response in a model of Helicobacter hepaticus-induced colitis

De Cicco, P., Sanders, T., Cirino, G., Maloy, K. J. and Ianaro, A. (2018) Hydrogen sulfide reduces myeloid-derived suppressor cell-mediated inflammatory response in a model of Helicobacter hepaticus-induced colitis. Frontiers in Immunology, 9, 499. (doi: 10.3389/fimmu.2018.00499) (PMID:29636751) (PMCID:PMC5880908)

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Abstract

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: CD11b+Ly6G+Ly6Clow with granulocytic phenotype (G-MDSCs) and CD11b+Ly6G−Ly6Chigh with monocytic phenotype (M-MDSCs). Hydrogen sulfide (H2S) 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 H2S pathway in innate immune-mediated IBD has not yet been elucidated. To better define a possible link between MDSCs and H2S pathway in colitis-associated CRC development, we used an innate immune-mediated IBD model induced by infection with the bacterium Helicobacter hepaticus (Hh), 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 Hh-infected mice. Following, we observed that chronic oral administration of the H2S donor DATS reduced colon inflammation by limiting the recruitment of G-MDSCs in the colon of Hh-infected mice. Thus, we identify the metabolic pathway l-cysteine/H2S as a possible new player in the immunosuppressive mechanism responsible for the MDSCs-promoted colitis-associated cancer development.

Item Type:Articles
Additional Information:This study was funded by Italian Government Grants, PRIN 2012 no: 2012WBSSY4_005.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maloy, Professor Kevin
Authors: De Cicco, P., Sanders, T., Cirino, G., Maloy, K. J., and Ianaro, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Frontiers in Immunology
Publisher:Frontiers Media
ISSN:1664-3224
ISSN (Online):1664-3224
Published Online:27 March 2018
Copyright Holders:Copyright © 2018 De Cicco, Sanders, Cirino, Maloy and Ianaro.
First Published:First published in Frontiers in Immunology 9:499
Publisher Policy:Reproduced under a Creative Commons license

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