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Extracellular matrix proteins regulate NK cell function in peripheral tissues
- Source :
- Science advances. 8(11)
- Publication Year :
- 2022
-
Abstract
- 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.
Details
- ISSN :
- 23752548
- Volume :
- 8
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Science advances
- Accession number :
- edsair.doi.dedup.....ee049d25f146de87de17cc52353fbafc