Transforming growth factor-beta 1 (TGF-beta 1) down-regulates IgA Fc-receptor (CD89) expression on human monocytes

IgA is the predominant immunoglobulin in human secretions and the second most important immunoglobulin in the circulation on a quantitative basis. The clearance of IgA is dependent on the function of at least three types of receptors. One of these receptors recognizes the Fc portion of the IgA molecule, Fc alpha R, which has been cloned recently. Fc alpha R, also designated CD89, is found on a number of cells, including human glomerular mesangial cells, and monocytes. In this study we analysed the effect of TGF-beta 1, a cytokine with strong immunosuppressive function, on the expression of CD89 on freshly isolated monocytes. We found that TGF-beta 1 down-regulates CD89 expression on human peripheral blood monocytes in a dose-dependent fashion. Optimal down-regulation occurred at a concentration of 5 ng/ml. The down-regulation of CD89 by TGF-beta 1 is linear in time, with a mean down-regulation of 34 +/- 13% after 24 h. Also at the mRNA level, CD89 expression was down-regulated by TGF-beta 1, suggesting regulation of CD89 at the transcriptional level. Monocytes pre-treated with TGF-beta 1 displayed a reduced response to IgA, as measured by IL-6 production by monocytes, in contrast to monocytes pre-treated with medium alone. These results suggest an important role for TGF-beta 1 in the regulation of CD89. This down-regulation may have direct consequences for the handling of IgA by human monocytes.