Leukocyte-Associated Ig-like Receptor-1–Deficient Mice Have an Altered Immune Cell Phenotype

Abstract

Cross-linking of the collagen binding receptor LAIR-1 in vitro delivers an inhibitory signal that is able to down-regulate activation-mediated signals. To study the in vivo function of LAIR-1, we generated LAIR-1−/− mice. They are healthy and fertile, and have normal longevity; however, they show certain phenotypic characteristics distinct from wild-type mice, including increased numbers of splenic B, T regulatory and dendritic cells. As LAIR-1−/− mice age, the splenic T cell population shows a higher frequency of activated and memory T cells. Since LAIR-1+/+ and LAIR-1−/− T cells traffic with equal proficiency to peripheral lymphoid organs, this is not likely due to abnormal T lymphocyte trafficking. LAIR-1−/− mice have lower serum levels of IgG1 and, in response to T-dependent immunization with TNP-OVA, switch less efficiently to antigen specific IgG2a and IgG2b, while switching to IgG1 is not affected. Several mouse disease models, including EAE and colitis, were utilized to examine the effect of LAIR-1 deficiency and no differences in the responses of LAIR-1−/− and LAIR-1+/+ mice were observed. Taken together, these observations indicate that LAIR-1 plays a role in regulating immune cells and suggest that any adverse effects of its absence may be balanced in vivo by other inhibitory receptors.

C1q limits dendritic cell differentiation and activation by engaging LAIR-1

“…A recent study reported the phenotype of LAIR-1-deficient C57BL/6 mice (27). These mice did not develop a lupus-like phenotype.…”

Enhanced efferocytosis by dendritic cells underlies memory T-cell expansion and susceptibility to autoimmune disease in CD300f-deficient mice

“…c-kit + cells isolated from bone marrow were cultured with 20 ng/ml GM-CSF and 20 ng/ml IL-4 for 6 days to generate the BMDC. 62 BMDC (2 × 10 5 ) were incubated with pHrodo-labeled AC at a ratio of 1:3 for 30, 60 and 120 min at 37°C, and then stained with anti-mouse CD11c for the phagocytosis analysis by flow cytometry as described for BMM cells. For the .…”

Inhibitory leukocyte immunoglobulin-like receptors in cancer development

“…Inhibition of expression of LAIR1 in human AML cell lines almost completely abolished leukemia development in xenografted NOD/SCID/IL2Rnull (NSG) mice [26]. In contrast, the studies of individual knockout mouse lines of PirB and gp49B1 (the only mouse orthologs) and of the LAIR1-knockout mouse revealed no overt defects in normal hematopoiesis [21,57,58].…”

“…LAIR1 does not affect normal hematopoiesis but is essential for leukemia development [26,38,57]. LAIR1 is a type I transmembrane glycoprotein that shares the same domain organization as LILRBs, containing one extracellular Ig-like domain that binds collagens or surfactant protein D and two intracellular ITIMs that recruit SHP-1 and SHP-2 [22][23][24][25].…”