IL-1β regulates a novel myeloid-derived suppressor cell subset that impairs NK cell development and function.
Chronic inflammation is associated with promotion of malignancy and tumor progression. Many tumors enhance the accumulation of myeloid-derived suppressor cells (MDSC), which contribute to tumor progression and growth by suppressing anti-tumor immune responses. Tumor-derived IL-1β secreted into the tumor microenvironment has been shown to induce the accumulation of MDSC possessing an enhanced capacity to suppress T cells. In this study, we found that the enhanced suppressive potential of IL-1β-induced MDSC was due to the activity of a novel subset of MDSC lacking Ly6C expression. This subset was present at low frequency in tumor-bearing mice in the absence of IL-1β-induced inflammation; however, under inflammatory conditions, Ly6C(neg) MDSC were predominant. Ly6C(neg) MDSC impaired NK cell development and functions in vitro and in vivo. These results identify a novel IL-1β-induced subset of MDSC with unique functional properties. Ly6C(neg) MDSC mediating NK cell suppression may thus represent useful targets for therapeutic interventions.
Innate Immunity Unit, Institut Pasteur, Paris, France.
Moshe
M
Elkabets
Vera S G
VS
Ribeiro
Charles A
CA
Dinarello
Suzanne
S
Ostrand-Rosenberg
James P
JP
Di Santo
Ron N
RN
Apte
Christian A J
CA
Vosshenrich
D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000378:metabolism; D000950:Antigens, Ly / Q000096:biosynthesis; D002277:Carcinoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D007108:Immune Tolerance; D007157:Immunologic Surveillance; D018836:Inflammation Mediators / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019139:Tumor Escape
D000943:Antigens, Differentiation; D000950:Antigens, Ly; D018836:Inflammation Mediators; D053583:Interleukin-1beta; C494192:Ly-6C antigen, mouse