CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages Export

@article{citeulike:2742994, abstract = {CD4+CD25+Foxp3+ regulatory T cells (Tregs) are potent suppressors of the adaptive immune system, but their effects on innate immune cells are less well known. Here we demonstrate a previously uncharacterized function of Tregs, namely their ability to steer monocyte differentiation toward alternatively activated macrophages (AAM). AAM are cells with strong antiinflammatory potential involved in immune regulation, tissue remodeling, parasite killing, and tumor promotion. We show that, after coculture with Tregs, monocytes/macrophages display typical features of AAM, including up-regulated expression of CD206 (macrophage mannose receptor) and CD163 (hemoglobin scavenger receptor), an increased production of CCL18, and an enhanced phagocytic capacity. In addition, the monocytes/macrophages have reduced expression of HLA-DR and a strongly reduced capacity to respond to LPS in terms of proinflammatory mediator production (IL-1, IL-6, IL-8, MIP-1{alpha}, TNF-{alpha}), NF{kappa}B activation, and tyrosine phosphorylation. Mechanistic studies reveal that CD4+CD25+CD127lowFoxp3+ Tregs produce IL-10, IL-4, and IL-13 and that these cytokines are the critical factors involved in the suppression of the proinflammatory cytokine response. In contrast, the Treg-mediated induction of CD206 is entirely cytokine-independent, whereas the up-regulation of CD163, CCL18, and phagocytosis are (partly) dependent on IL-10 but not on IL-4/IL-13. Together these data demonstrate a previously unrecognized function of CD4+CD25+Foxp3+ Tregs, namely their ability to induce alternative activation of monocytes/macrophages. Moreover, the data suggest that the Treg-mediated induction of AAM partly involves a novel, cytokine-independent pathway. 10.1073/pnas.0706832104}, author = {Tiemessen, Machteld M. and Jagger, Ann L. and Evans, Hayley G. and van Herwijnen, Martijn J. and John, Susan and Taams, Leonie S.}, citeulike-article-id = {2742994}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0706832104}, citeulike-linkout-1 = {http://www.pnas.org/content/104/49/19446.full.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/104/49/19446.full.full.pdf}, citeulike-linkout-3 = {http://www.pnas.org/cgi/content/abstract/104/49/19446}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/18042719}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=18042719}, day = {4}, doi = {10.1073/pnas.0706832104}, journal = {Proceedings of the National Academy of Sciences}, keywords = {immune, innate, macrophage, monocytes, system, treg}, month = {December}, number = {49}, pages = {19446--19451}, posted-at = {2009-02-10 23:57:28}, priority = {2}, title = {CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages}, url = {http://dx.doi.org/10.1073/pnas.0706832104}, volume = {104}, year = {2007} }

TY - JOUR ID - citeulike:2742994 L3 - citeulike-article-id:2742994 N2 - CD4+CD25+Foxp3+ regulatory T cells (Tregs) are potent suppressors of the adaptive immune system, but their effects on innate immune cells are less well known. Here we demonstrate a previously uncharacterized function of Tregs, namely their ability to steer monocyte differentiation toward alternatively activated macrophages (AAM). AAM are cells with strong antiinflammatory potential involved in immune regulation, tissue remodeling, parasite killing, and tumor promotion. We show that, after coculture with Tregs, monocytes/macrophages display typical features of AAM, including up-regulated expression of CD206 (macrophage mannose receptor) and CD163 (hemoglobin scavenger receptor), an increased production of CCL18, and an enhanced phagocytic capacity. In addition, the monocytes/macrophages have reduced expression of HLA-DR and a strongly reduced capacity to respond to LPS in terms of proinflammatory mediator production (IL-1, IL-6, IL-8, MIP-1{alpha}, TNF-{alpha}), NF{kappa}B activation, and tyrosine phosphorylation. Mechanistic studies reveal that CD4+CD25+CD127lowFoxp3+ Tregs produce IL-10, IL-4, and IL-13 and that these cytokines are the critical factors involved in the suppression of the proinflammatory cytokine response. In contrast, the Treg-mediated induction of CD206 is entirely cytokine-independent, whereas the up-regulation of CD163, CCL18, and phagocytosis are (partly) dependent on IL-10 but not on IL-4/IL-13. Together these data demonstrate a previously unrecognized function of CD4+CD25+Foxp3+ Tregs, namely their ability to induce alternative activation of monocytes/macrophages. Moreover, the data suggest that the Treg-mediated induction of AAM partly involves a novel, cytokine-independent pathway. 10.1073/pnas.0706832104 IS - 49 JF - Proceedings of the National Academy of Sciences EP - 19451 TI - CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages VL - 104 SP - 19446 KW - immune KW - innate KW - macrophage KW - monocytes KW - system KW - treg AU - Tiemessen, Machteld AU - Jagger, Ann AU - Evans, Hayley AU - van Herwijnen, Martijn AU - John, Susan AU - Taams, Leonie PY - 2007/12/04/ UR - http://dx.doi.org/10.1073/pnas.0706832104 ER -