Fig. 4

Immunostimulatory vs. immunoregulatory functions of pDCs. In both lymphoid and nonlymphoid organs, pDCs are involved in various biological and pathological processes in addition to their contribution to antiviral defense. pDCs can exert immunostimulating (IFN production) or immunoregulatory (promotion of Treg cells) functions, which can be beneficial (green) or detrimental (red) for the host, depending on the context. For example, pDCs recruited to the skin upon tissue damage promote tissue repair through IFN production, but when dysregulated, this function can be deleterious, promoting skin pathologies and autoimmune diseases. pDCs might be detrimental in bone marrow thrombocytopenia, by inhibiting proplatelet release due to the pathological loss of SiglecH-dependent inhibition of pDC IFN production. How this process might be beneficial and in what pathophysiological context are unknown. The role of pDCs in the large intestine depends on the pathological context and is still controversial. Immunoregulatory pDCs that produce anti-inflammatory cytokines, such as IL-10 or TGF-β, can benefit the host in different contexts. At a steady state, they can promote the expansion of CD4+ Tregs, contributing to central tolerance in the thymus and to oral tolerance in the liver and small intestine. During neuroinflammation, the recruitment of immunoregulatory pDCs to the brain can dampen inflammatory responses and ameliorate tissue lesions