CD49d is a new marker for distinct myeloid-derived suppressor cell subpopulations in mice.
Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of cells that negatively regulate the immune response during tumor progression, inflammation, and infection. In this study, through gene-expression analysis, we have identified a new marker, CD49d, which is expressed exclusively on CD11b(+)Gr-1(dull/int.) MDSCs. We have characterized two subpopulations of MDSCs based on CD49d expression in two different settings, a mouse model of inflammatory bowel disease and tumor-bearing mice. The CD49d(+) subset of MDSCs was mainly monocytic and strongly suppressed Ag-specific T cell proliferation in an NO-dependent mechanism similar to Gr-1(dull/int.) MDSCs. Alternatively, CD49d(-) cells were granulocytic and poorly inhibited T cell proliferation compared with CD11b(+)Gr-1(high) cells. Both mouse models showed preferential expansion of the granulocytic CD49d(-) subset. We suggest that CD49d can be used as an alternative marker for Gr-1 to differentiate between the subpopulations of MDSCs together with CD11b, which will ultimately help in understanding the mechanisms of immune suppression by MDSCs.
Haile
Lydia A
LA
Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, Germany.
Gamrekelashvili
Jaba
J
Manns
Michael P
MP
Korangy
Firouzeh
F
Greten
Tim F
TF
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D039481:CD11b Antigen / Q000096:biosynthesis / Q000502:physiology; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D016130:Immunophenotyping; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology; D039441:Integrin alpha4 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology; D009569:Nitric Oxide / Q000502:physiology; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; D039481:CD11b Antigen; D018984:Epitopes, T-Lymphocyte; C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine; D039441:Integrin alpha4; D009569:Nitric Oxide