In:
The Journal of Immunology, The American Association of Immunologists, Vol. 188, No. 1_Supplement ( 2012-05-01), p. 167.1-167.1
Abstract:
Leukocyte-associated inhibitory receptor (LAIR)-1 is a collagen receptor. Cross-linking of LAIR-1 suppresses the differentiation of dendritic cells (DCs). We found that C1q, which is known to have an inhibitory role in the differentiation of DCs, maintained the expression of LAIR-1 in cells transitioning between monocytes and DCs. Since C1q contains a collagen-like tail, we hypothesized that a C1q/LAIR-1 interaction leads to DC lineage arrest. In order to assess interactions between C1q and LAIR-1, we explored three models. First, HEK293T cells were transfected with a plasmid encoding LAIR-1. Labeled C1q associated with LAIR-1 expressing cells in a dose specific manner; this binding was inhibited by soluble LAIR-2, which exhibits the same collagen binding capacity as LAIR-1. Second, THP-1 cells, a LAIR-1hi human monocytic leukemia cell line, exhibited a high degree of binding to C1q which was also blocked by sLAIR-2. Third, in primary human monocytes, sLAIR-2 blocked the effects of C1q on monocyte-derived DC differentiation. We confirmed a direct interaction between C1q and LAIR-1 by dot blot analysis. Moreover, LAIR-1 was phosphorylated in a C1q-dependent manner in primary monocytes, demonstrating that C1q is an inducer of LAIR-1/ITIM-specific phosphorylation. Collectively, these data indicate that C1q functions as a natural ligand for LAIR-1. These findings provide novel insights into how C1q may prevent unwarranted immune responses.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.188.Supp.167.1
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2012
detail.hit.zdb_id:
1475085-5
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