CD163 macrophages suppress CD8 and NK cells through CD163 mediated HLA-E (H2-T23)

CD163 macrophages, which can be identified in different tissues of individuals such as the colon and tumor tissues, possessed markedly immunosuppressive functions on immune cells, especially effective cells such as CD8 cells. However, the mechanism(s) by which CD163 macrophages inhibit immune responses remains to be illusive. Using single cell-sequence techniques, we identified CD163+ macrophage subset in the colon tissues. Meanwhile, we also characterized CD163+ macrophage associated immune cell populations and subpopulations in mouse colon tissues. Deletion of CD163+ macrophage subset could markedly increase the proportions of CD8 and NK cells. Mechanistically, CD163+ macrophage subpopulations can inhibit the proliferation of CD8 and NK cells through inhibitory molecules CD94/NKG2a (KLRD1/KLRC1 in mice) and their ligand HLA-E /H2-T23 (Human/mice) on the surface of CD163+ macrophages. Importantly, CD163 in macrophages could promote the expression of HLA-E/H2-T23 expression through inducing the expression of signal peptide peptidase (SPP), offering a target for immunotherapy in CD8 and NK cells associated immunosuppressive diseases such as tumor. Taken together, we demonstrate that CD163+macrophage subpopulation plays a critical role in suppressing CD8 and NK cells through CD163 mediated HLA-E/H2-T23. Peripheral blood monocytes were infected with CD163 shRNA lentivirus and shNC control lentivirus, and cultured for 5 days in the presence of M-CSF. Total RNA was then extracted for high-throughput sequencing.