Development of a nascent galectin-1 chimeric molecule for studying the role of leukocyte galectin-1 ligands and immune disease modulation.
Development of a nascent galectin-1 chimeric molecule for studying the role of leukocyte galectin-1 ligands and immune disease modulation.
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DOI：
10.4049/jimmunol.1000715
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发表时间：
2010-10-15
期刊：
影响因子：
--
通讯作者：
Dimitroff CJ
中科院分区：
文献类型：
--
作者：
Cedeno-Laurent F;Barthel SR;Opperman MJ;Lee DM;Clark RA;Dimitroff CJ
Galectin-1 (Gal-1), a β-galactoside–binding lectin, plays a profound role in modulating adaptive immune responses by altering the phenotype and fate of T cells. Experimental data showing recombinant Gal-1 (rGal-1) efficacy on T cell viability and cytokine production, nevertheless, is controversial due to the necessity of using stabilizing chemicals to help retain Gal-1 structure and function. To address this drawback, we developed a mouse Gal-1 human Ig chimera (Gal-1hFc) that did not need chemical stabilization for Gal-1 ligand recognition, apoptosis induction, and cytokine modulation in a variety of leukocyte models. At high concentrations, Gal-1hFc induced apoptosis in Gal-1 ligand+ Th1 and Th17 cells, leukemic cells, and granulocytes from synovial fluids of patients with rheumatoid arthritis. Importantly, at low, more physiologic concentrations, Gal-1hFc retained its homodimeric form without losing functionality. Not only did Gal-1hFc–binding trigger IL-10 and Th2 cytokine expression in activated T cells, but members of the CD28 family and several other immunomodulatory molecules were upregulated. In a mouse model of contact hypersensitivity, we found that a non-Fc receptor-binding isoform of Gal-1hFc, Gal-1hFc2, alleviated T cell-dependent inflammation by increasing IL-4+, IL-10+, TGF-β +, and CD25high/FoxP3+ T cells, and by decreasing IFN-γ + and IL-17+ T cells. Moreover, in human skin-resident T cell cultures, Gal-1hFc diminished IL-17+ T cells and increased IL-4+ and IL-10+ T cells. Gal-1hFc will not only be a useful new tool for investigating the role of Gal-1 ligands in leukocyte death and cytokine stimulation, but for studying how Gal-1–Gal-1 ligand binding shapes the intensity of immune responses.
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DOI：
10.1073/pnas.0706017104
发表时间：
2007-08-07
影响因子：
11.1
作者：
Juszczynski, Przemyslaw;Ouyang, Jing;Shipp, Margaret A.
通讯作者：
Shipp, Margaret A.
影响因子：
82.9
作者：
Blois, Sandra M.;Ilarregui, Juan M.;Arck, Petra C.
通讯作者：
Arck, Petra C.
影响因子：
2.7
作者：
Howard, MR;Lodge, AP;Moss, DJ
通讯作者：
Moss, DJ
影响因子：
20.3
作者：
Clark, Rachael A.;Kupper, Thomas S.
通讯作者：
Kupper, Thomas S.
影响因子：
20.3
作者：
Garin, Marina I.;Chu, Chung-Ching;Lechler, Robert I.
通讯作者：
Lechler, Robert I.