Interleukin-10 induces macrophage apoptosis and expression of CD16 (Fc gamma RIII) whose engagement blocks the cell death programme and facilitates differentiation

The development of monocytes into macrophages is regulated by helper T cell s (Th) cells and, vice versa, the differentiation of Th cells into Th1 and Th2 is regulated by macrophages. Herein we examined the role of the Th2 cyt okine, interleukin-10 (IL-10), on the development of macrophages. IL-10 is known to block the expression of antigen-presenting major histocompatibilit y complex (MHC) II and of costimulatory B7 molecules but it induces the exp ression of FcRs, especially the Fc gamma RIII (CD16). The expression of CD1 6 enables the macrophage to carry out antibody-dependent cell-mediated cyto toxicity (ADCC) functions. However, this differentiation step is largely un dercut by the capacity of IL-10 to induce macrophage apoptosis before the p rocess of differentiation ensues. We found that the negative effect of IL-1 0 on the survival of macrophages is reversed in an environment that contain s immunoglobulin C (IgG). IgG, especially when immune complexed with antige n, stimulates CD16 to transmit survival signals in macrophages which enable them to complete the differentiation process into CD16(+) cells. Thus. IL- 10 suppresses macrophage accumulation in healthy tissues where IgG is absen t, and Facilitates macrophage accumulation and differentiation in tissues t hat contain IgG, for example inflamed tissues or tissues that present autor eactive antibodies.