Characterisation of murine MICL (CLEC12A) and evidence for an endogenous ligand

被引:57
作者
Pyz, Elwira [1 ]
Huysamen, Cristal [1 ]
Marshall, Andrew S. J. [2 ]
Gordon, Siamon [2 ]
Taylor, Philip R. [3 ]
Brown, Gordon D. [1 ]
机构
[1] Univ Cape Town, Inst Infect Dis & Mol Med, Div Immunol, ZA-7925 Cape Town, South Africa
[2] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
[3] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff, Wales
基金
英国医学研究理事会; 英国惠康基金;
关键词
c-type lectin; endogenous ligand; inhibitory receptors; myeloid cell; myeloid inhibitory c-type lectin;
D O I
10.1002/eji.200738057
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
inhibitory receptors are required for the control of cellular activation and they play essential roles in regulating homeostasis and immunity. We previously identified a human inhibitory C-type lectin-like receptor, MICL (CLEC12A), a heavily glycosylated monomer predominantly expressed on myeloid cells. Here we characterise the murine homolog of MICL (mMICL), and demonstrate that the receptor is structurally and functionally similar to the human orthologue (hMICL), although there are some notable differences. mMICL is expressed as a dimer and is not heavily glycosylated; however, like hMICL, the receptor can recruit inhibitory phosphatases upon activation, and is down-regulated on leukocytes following stimulation with selected TLR agonists. Using novel monoclonal antibodies, we demonstrate that, like the human receptor, mMICL is predominantly expressed by myeloid cells. However, mMICL is also expressed by B cells and CD8(+) T cells in peripheral blood, and NK cells in the bone marrow. Finally, we show that mMICL recognises an endogenous ligand in a variety of murine tissues, suggesting that the receptor plays a role in homeostasis.
引用
收藏
页码:1157 / 1163
页数:7
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