Characterisation of the bovine C-type lectin receptor Mincle and potential evidence for an endogenous ligand 1
Characterisation of the bovine C-type lectin receptor Mincle and potential evidence for an endogenous ligand 1
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牛 C 型凝集素受体 Mincle 的表征和内源配体的潜在证据 1
DOI：
10.1101/2023.03.20.533273
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发表时间：
2023
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与次级受体形成复合物的先天免疫受体，激活多种信号传导途径，调节细胞活化，并在调节体内平衡和免疫中发挥重要作用。我们以前已经确定了各种牛C型凝集素样受体，具有类似的功能，比他们的人类直系同源物。Mincle（CLEC 4 E）是一种高度糖基化的单体，参与识别分枝杆菌组分Cord因子（海藻糖6，6 ′-二霉菌酸酯）。在这里，我们将牛的同源物Mincle（boMincle），并证明该受体的结构和功能类似于人类的直系同源物（huMincle），虽然有一些显着的差异。在没有交叉反应抗体的情况下，产生了boMincle特异性抗体，并用于证明与人受体一样，boMincle主要由骨髓细胞表达。BoMincle表面表达在单核细胞成熟为巨噬细胞期间增加。然而，在粒细胞、B细胞和T细胞中也检测到boMincle mRNA转录物。最后，我们表明，boMincle结合到分离的牛CD 4 +T细胞以特定的方式，表明有潜力识别内源性配体。这表明该受体也可能在牛的体内平衡中发挥作用。
Innate immune receptors that form complexes with secondary receptors, activating multiple signalling pathways, modulate cellular activation and play essential roles in regulating homeostasis and immunity. We have previously identified a variety of bovine C-type lectin-like receptors that possess similar functionality than their human orthologues. Mincle (CLEC4E), a heavily glycosylated monomer, is involved in the recognition of the mycobacterial component Cord factor (trehalose 6,6′-dimycolate). Here we characterise the bovine homologue of Mincle (boMincle), and demonstrate that the receptor is structurally and functionally similar to the human orthologue (huMincle), although there are some notable differences. In the absence of cross-reacting antibodies, boMincle-specific antibodies were created and used to demonstrate that, like the human receptor, boMincle is predominantly expressed by myeloid cells. BoMincle surface expression increases during the maturation of monocytes to macrophages. However, boMincle mRNA transcripts were also detected in granulocytes, B cells, and T cells. Finally, we show that boMincle binds to isolated bovine CD4+T cells in a specific manner, indicating the potential to recognise endogenous ligands. This suggests that the receptor might also play a role in homeostasis in cattle.