title: The role and potential therapeutic application of myeloid-derived suppressor cells in TNBS-induced colitis.
abstract: MDSCs, a heterogeneous population of cells that expand during many pathogenic conditions, have remarkable abilities to suppress T cell responses. Their role in murine colitis, induced by TNBS and therapeutic application, remains unclear. Murine colitis was induced through intrarectally administrating TNBS, twice. MDSCs in spleen and colonic LPMCs were identified using flow cytometric analysis. In adoptive transfer, MDSCs were isolated from spleen after TNBS challenges by using microbeads or generated in vitro by coculturing bone marrow cells with HSCs and then transferred into naïve mice. Two hours later, mice were then challenged with TNBS, once/week for 2 weeks. The mice were killed four days after the second TNBS delivery, and intestinal inflammation and cytokine levels and MDSC percentages were evaluated. The percentages of CD11b+Gr-1+MDSCs and subsets (CD11b+Ly6C+ and CD11b+Ly6G+MDSCs) were increased in spleen and/or colonic LPMCs in colitis mice and also correlated with the severity of intestinal inflammation. MDSCs isolated from colitis mice suppressed the proliferation of splenocytes in vitro. Adoptive transfer of MDSCs, isolated from colitis mice or generated in vitro, decreased intestinal inflammation, levels of IFN-γ, IL-17, and TNF, and percentages of spleen MDSCs when compared with controls. MDSCs that have inhibitory function in vitro and in vivo are increased and correlated with intestinal inflammation, suggesting that they may be used as a biomarker of disease activity and a cell-based biotherapy in IBD.
authors.affiliation: 1.University of Manitoba, 532-715 McDermot Ave., Winnipeg, Manitoba, Canada R3E 3P4. zpeng@mich.ca.
authors.forename: Qingdong
authors.initials: Q
authors.lastname: Guan
authors.forename: Sem
authors.initials: S
authors.lastname: Moreno
authors.forename: Gefei
authors.initials: G
authors.lastname: Qing
authors.forename: Carolyn R
authors.initials: CR
authors.lastname: Weiss
authors.forename: Lina
authors.initials: L
authors.lastname: Lu
authors.forename: Charles N
authors.initials: CN
authors.lastname: Bernstein
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Warrington
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Ma
authors.forename: Zhikang
authors.initials: Z
authors.lastname: Peng
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001835:Body Weight; D049109:Cell Proliferation; D002469:Cell Separation; D048430:Cell Shape; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D005260:Female; D055166:Hepatic Stellate Cells / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D022423:Myeloid Cells / Q000378:metabolism / Q000637:transplantation*; D013154:Spleen / Q000473:pathology; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D016207:Cytokines; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate
keywords: cell-based immunotherapy; immune down-regulation; inflammatory bowel disease; murine colitis