| First Author | Bunting MD | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 11 | Pages | eabk3327 |
| PubMed ID | 35294229 | Mgi Jnum | J:322849 |
| Mgi Id | MGI:7259530 | Doi | 10.1126/sciadv.abk3327 |
| Citation | Bunting MD, et al. (2022) Extracellular matrix proteins regulate NK cell function in peripheral tissues. Sci Adv 8(11):eabk3327 |
| abstractText | Natural killer (NK) cells reject major histocompatibility complex class I (MHC-I)-deficient bone marrow through direct cytotoxicity but not solid organ transplants devoid of MHC-I. Here, we demonstrate an immediate switch in NK cell function upon exit from the circulation, characterized by a shift from direct cytotoxicity to chemokine/cytokine production. In the skin transplant paradigm, combining an NK cell-specific activating ligand, m157, with missing self MHC-I resulted in complete graft rejection, which was dependent on NK cells as potential helpers and T cells as effectors. Extracellular matrix proteins, collagen I, collagen III, and elastin, blocked NK cell cytotoxicity and promoted their chemokine/cytokine production. NK cell cytotoxicity against MHC-I-deficient melanoma in the skin was markedly increased by blocking tumor collagen deposition. MHC-I down-regulation occurred in solid human cancers but not leukemias, which could be directly targeted by circulating cytotoxic NK cells. Our findings uncover a fundamental mechanism that restricts direct NK cell cytotoxicity in peripheral tissues. |
