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TGF-beta 1 suppresses [correction of supresses] myeloid Fc gamma receptor function by regulating the expression and function of the common gamma-subunit

Tridandapani, S.; Wardrop, R.; Baran, C.P.; Wang, Y.; Opalek, J.M.; Caligiuri, M.A.; Marsh, C.B.

Journal of Immunology 170(9): 4572-4577

2003


ISSN/ISBN: 0022-1767
PMID: 12707335
Accession: 011449859

We have previously reported that FcgammaR-mediated function in myeloid cells is a tightly regulated event that is influenced by the cytokines present in the milieu. TGF-beta1 is an immunosuppressive cytokine with pleiotropic effects on immune responses; however, the molecular mechanism by which TGF-beta suppresses immune responses is poorly understood. In this study, we have analyzed the effect of TGF-beta on FcgammaR-mediated activation of myeloid cells. We report that TGF-beta1-treated THP-1 human myeloid cells displayed reduced ability to phagocytose IgG-coated particles. Because FcgammaR expression is modulated by cytokines, we analyzed expression levels of FcgammaRI, FcgammaRIIa, FcgammaRIIb, and FcgammaRIIIa in cells cultured with or without TGF-beta1 and found while total protein levels of the FcgammaR were not reduced, surface expression of FcgammaRI and FcgammaRIII was lower in cells cultured with TGF-beta1. Concomitantly, there was a dose-dependent reduction in the expression of the FcgammaR-associated gamma-subunit. This suppressive effect of TGF-beta was likewise observed in bone marrow-derived murine myeloid cells and human monocytes. Importantly, TGF-beta1 also significantly reduced the production of monocyte chemoattractant protein-1 induced by immobilized IgG, which would further reduce monocyte recruitment to the site of inflammation. In contrast, human alveolar macrophages were refractory to this effect, expressing low levels of TGF-beta type II receptors compared with peripheral blood monocytes from the same donor. These data provide insight into the regulation of immune responses by TGF-beta1 and demonstrate the selectivity of these effects.

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