Back to Search
Start Over
Leukocyte-Associated Ig-like Receptor 1 Inhibits T h 1 Responses but Is Required for Natural and Induced Monocyte-Dependent T h 17 Responses.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2018 Jul 15; Vol. 201 (2), pp. 772-781. Date of Electronic Publication: 2018 Jun 08. - Publication Year :
- 2018
-
Abstract
- 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 <subscript>h</subscript> 1 responses were enhanced as predicted, T <subscript>h</subscript> 17 responses were strongly inhibited. Indeed, LAIR1 on both T cells and monocytes was required for optimal T <subscript>h</subscript> 17 responses to collagen type (Col)V. For pre-existing "natural" T <subscript>h</subscript> 17 response to ColV, the LAIR1 requirement was absolute, whereas adaptive T <subscript>h</subscript> 17 and T <subscript>h</subscript> 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 <subscript>h</subscript> 1 responses in a dose-dependent manner, but it had no effect on T <subscript>h</subscript> 17 responses. In IL-17-dependent murine organ transplant models of chronic rejection, LAIR1 <superscript>+/+</superscript> but not LAIR1 <superscript>-/-</superscript> littermates mounted strong fibroproliferative responses. Surface LAIR1 expression was higher on human T <subscript>h</subscript> 17 cells as compared with T <subscript>h</subscript> 1 cells, ruling out a receptor deficiency that could account for the differences. We conclude that LAIR1 ligation by its natural ligands favors T <subscript>h</subscript> 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 <subscript>h</subscript> 17 over T <subscript>h</subscript> 1 development, posing a risk to long-term graft survival.<br /> (Copyright © 2018 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
Autoantigens immunology
Cells, Cultured
Collagen metabolism
Humans
Immunity, Cellular
Immunomodulation
Interleukin-17 immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Monocytes immunology
Organ Transplantation
Protein Binding
Receptors, Immunologic genetics
Graft Rejection immunology
Receptors, Immunologic metabolism
Th1 Cells physiology
Th17 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 201
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 29884698
- Full Text :
- https://doi.org/10.4049/jimmunol.1701753