Leucocyte-associated immunoglobulin-like receptor-1 is an inhibitory regulator of contact hypersensitivity.
Leucocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a membrane receptor of the immunoglobulin (Ig) superfamily that is expressed on most types of haematopoietic cells, and delivers inhibitory signals through interacting with collagens. In order to elucidate the immunological functions of LAIR-1 in vivo, we established transgenic mice expressing a chimeric protein composed of the extracellular domain of LAIR-1 fused with an Ig tag (LAIR-1-Ig), which acts as a decoy by competing with endogenous LAIR-1. The transgenic mice showed an increased susceptibility for development of contact hypersensitivity (CHS), an experimental model of allergic contact dermatitis, in association with enhanced hapten-specific T-cell responses. When T cells from the hapten-sensitized donor mice were transferred into non-sensitized recipients, treatment of either donor mice or recipient mice with LAIR-1-Ig protein accelerated CHS, suggesting a potentially negative role of LAIR-1 in both the sensitization and the elicitation of hapten-reactive T cells. In vitro assays revealed that LAIR-1 decreased the production of interleukin-6 and interleukin-12 in dendritic cells, and inhibited the proliferation and cytokine production of naïve and memory T cells along with G(0)/G(1) cell cycle arrest. Collectively, our findings suggest that LAIR-1 plays a crucial inhibitory role in CHS by regulating antigen-presenting cell and T-cell functions.
Omiya
Ryusuke
R
Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA.
Tsushima
Fumihiko
F
Narazaki
Hidehiko
H
Sakoda
Yukimi
Y
Kuramasu
Atsuo
A
Kim
Youn
Y
Xu
Haiying
H
Tamura
Hideto
H
Zhu
Gefeng
G
Chen
Lieping
L
Tamada
Koji
K
D000818:Animals; D002453:Cell Cycle / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000172:deficiency; D003713:Dendritic Cells / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D006241:Haptens / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011971:Receptors, Immunologic / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D016207:Cytokines; D004268:DNA-Binding Proteins; D006241:Haptens; C499308:Rag2 protein, mouse; D011971:Receptors, Immunologic; C108073:leukocyte-associated immunoglobulin-like receptor 1