IL-1β regulates a novel myeloid-derived suppressor cell subset that impairs NK cell development and function

Moshe Elkabets (1, 2) , Vera S. G. Ribeiro (3, 1) , Charles A Dinarello (4) , Suzanne Ostrand-Rosenberg (5) , James P Di Santo (1) , Ron Apte (2) , Christian A. J. Vosshenrich (1)

1 Immunité Innée
2 Shraga Segal Department of Microbiology and Immunology, The Cancer Research Center,
3 PhD Programme in Experimental Biology and Biomedicine, Center for Neurosciences and Cell Biology, University of Coimbra
4 Department of Medicine [Denver]
5 Department of Biological Sciences [Baltimore]

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.

Domaines: Immunité innée

Moshe Elkabets, Vera S. G. Ribeiro, Charles A Dinarello, Suzanne Ostrand-Rosenberg, James P Di Santo, et al.. IL-1β regulates a novel myeloid-derived suppressor cell subset that impairs NK cell development and function. European Journal of Immunology, 2010, ⟨10.1002/eji.201041037⟩. ⟨hal-01370734⟩