Interleukin‐10 induces macrophage apoptosis and expression of CD16 (FcγRIII) whose engagement blocks the cell death programme and facilitates differentiation

The development of monocytes into macrophages is regulated by helper T cells (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 cytokine, interleukin-10 (IL-10), on the development of macrophages. IL-10 is known to block the expression of antigen-presenting major histocompatibility complex (MHC) II and of costimulatory B7 molecules but it induces the expression of FcRs, especially the FcgammaRIII (CD16). The expression of CD16 enables the macrophage to carry out antibody-dependent cell-mediated cytotoxicity (ADCC) functions. However, this differentiation step is largely undercut by the capacity of IL-10 to induce macrophage apoptosis before the process of differentiation ensues. We found that the negative effect of IL-10 on the survival of macrophages is reversed in an environment that contains immunoglobulin G (IgG). IgG, especially when immune complexed with antigen, 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 absent, and facilitates macrophage accumulation and differentiation in tissues that contain IgG, for example inflamed tissues or tissues that present autoreactive antibodies.