期刊
JOURNAL OF IMMUNOLOGY
卷 201, 期 2, 页码 772-781出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1701753
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- National Institutes of Health [1P01AI084853, 1R01AI119140, R01AI110617]
Leukocyte-associated Ig-like receptor 1 (LAIR1) is an ITIM-bearing collagen receptor expressed by leukocytes and is implicated in immune suppression. However, using a divalent soluble LAIR1/Fc recombinant protein to block interaction of cell surface LAIR1 with matrix collagen, we found that whereas T(h)1 responses were enhanced as predicted, T(h)17 responses were strongly inhibited. Indeed, LAIR1 on both T cells and monocytes was required for optimal T(h)17 responses to collagen type (Col) V. For pre-existing natural T(h)17 response to ColV, the LAIR1 requirement was absolute, whereas adaptive T(h)17 and T(h)1/17 immune responses in both mice and humans were profoundly reduced in the absence of LAIR1. Furthermore, the addition of C1q, a natural LAIR1 ligand, decreased T(h)1 responses in a dose-dependent manner, but it had no effect on T(h)17 responses. In IL-17-dependent murine organ transplant models of chronic rejection, LAIR1(+/+) but not LAIR1(-/-) littermates mounted strong fibroproliferative responses. Surface LAIR1 expression was higher on human T(h)17 cells as compared with T(h)1 cells, ruling out a receptor deficiency that could account for the differences. We conclude that LAIR1 ligation by its natural ligands favors T(h)17 cell development, allowing for preferential activity of these cells in collagen-rich environments. The emergence of cryptic self-antigens such as the LAIR1 ligand ColV during ischemia/reperfusion injury and early acute rejection, as well as the tendency of macrophages/monocytes to accumulate in the allograft during chronic rejection, favors T(h)17 over T(h)1 development, posing a risk to long-term graft survival.
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