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.
Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, Germany.
Lydia A
LA
Haile
Jaba
J
Gamrekelashvili
Michael P
MP
Manns
Firouzeh
F
Korangy
Tim F
TF
Greten
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