Dendritic cells (DCs) coordinate T cell activation versus T cell tolerance depending on the signals they receive from their environment. RORγt+ DCs have emerged as a new lineage of antigen presenting cells that regulate T cell tolerance in the intestine. We have shown that RORγt+ DCs are found across tissues and can also activate and induce the effector differentiation of naïve CD4+ T cells, suggesting a more versatile functional spectrum. Additionally, we found RORγt+ DCs to be FLT3L-dependent, which makes FLT3L an attractive target to expand these cells.
RORγt+ DCs are now recognized to exist as subtypes expressing varying levels of CD11c. Indeed, only CD11chi RORγt+ DCs are FLT3L-dependent. Various studies have tried to expand RORγt+ DCs by promoting FLT3L signaling and obtained conflicting results. We find considerable diversity in the expression of the FLT3L-receptor CD135 among RORγt+ DC subsets, possibly explaining limited expansion in prior studies. Using FLT3L injection in adult mice, we observe robust expansion of DCs and Flt3-expressing RORγt+ DC subsets, while expansion of RORγt-expressing type 3 innate lymphocytes (ILC3) is limited. Using this robust expansion protocol puts us in a situation to further probe the functions of RORγt+ DCs across different tissue environments.