Bone marrow-derived inflammatory and steady state DCs are different in both functions and survival

Abstract

Dendritic cells (DCs) contain heterogeneous populations, with classical DCs developed at steady state and monocyte-derived DCs mobilized under inflammatory conditions, although their total numbers in vivo are scares. To obtain enough quantity for immunological study or clinical application, we have previously established that bone marrow-derived DCs in the presence of Flt-3L (FL-DCs) or GM-CSF (GM-DCs) in vitro are equivalent to the steady state DCs and inflammatory DCs in vivo respectively. What difference, however, exists between these two most commonly used culture systems in DC functions and survival, and how does it correlate to the division of works by their corresponding counterparts in vivo remain ill-defined. In this study, we found that GM-DCs of inflammatory nature were more phagocytic, potent at inducing Th2 and Th17 differentiation, and had longer survival rate, whereas FL-DCs of steady state characters were stronger T cell activator and better at directing Th1 differentiation. Mechanistically, NO production induced by the LPS-activated GM-DCs could partly explain for their failure to improve T cell proliferation, and the distinct T cell differentiation profiles and viability demonstrated by the two types of DCs were underpinned by their preferential secretion of T cell polarizing cytokines and expression of anti-apoptotic genes. Such disparate functionalities and survival potentials of steady state and inflammatory DCs in vitro fit in well with their respective roles in vivo in particular immunological settings and have serious implications in translational applications.

Keywords: Dendritic cells; GM-CSF; Inflammation; T cell differentiation; T cell proliferation.