Plasmacytoid dendritic cells (pDC) are involved in innate immune response to viral infection. They can mount a strong anti-viral response with the release of high amount of type I IFN after recognition of pathogen-derived material. Since pDC demonstrate potent antigen (Ag) presentation capacity, they have been involved in adaptive immunity. Effector T cell polarization is highly dictates by the microenvironment created by the Ag presenting cell, itself affected by the microenvironment shaped during pathogen elimination. We demonstrated that pDC are critical cells in the tolerance mechanism to apoptotic cells. The microenvironment created by apoptotic cell favors pDC to induce Treg polarization. However, we demonstrated that sole TGF-β polarizes pDC to induce Th17 commitment. Thus we recently identified factors in the secretome of phagocytes eliminating apoptotic cells that prevent pDC to promote Th17 polarization but favor pDC to drive Treg commitment. Such factors implicate chemokine released by phagocytes eliminating apoptotic cells and chemokine receptor signaling in the pDC rendering pDC no longer sensitive to inflammatory stimulus. A lack in this pathway strongly induced inflammatory pDC and inhibited apoptotic cell-induced tolerance through pDC. Thus we identified a chemokine/chemokine receptor critical pathway that prevents inflammation to apoptotic bodies and therefore favor tolerance induction to apoptotic cells though the specific involvement of pDC.
- Copyright © 2013 by The American Association of Immunologists, Inc.