Cytip regulates dendritic-cell function in contact hypersensitivity.

ABSTRACT

Cytohesin-interacting protein (Cytip) is induced during dendritic cell (DC) maturation and in T cells upon activation. It has also been shown to be involved in the regulation of immune responses. Here, we evaluated the functional consequences of Cytip deficiency in DCs using Cytip knockout (KO) mice. No difference in DC subpopulations in the skin draining lymph nodes (LNs) was found between Cytip KO mice and their wild-type counterparts, excluding a role in DC development. To investigate the function of Cytip in DCs in vivo, we used 2,4,6-trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) as a model system. In the sensitization as well as in the elicitation phase, DCs derived from Cytip KO mice induced an increased inflammatory reaction indicated by more pronounced ear swelling. Furthermore, IL-12 production was increased in Cytip KO bone marrow-derived DCs (BMDCs) after CpG stimulation. Additionally, Cytip-deficient DCs loaded with ovalbumin induced stronger proliferation of antigen-specific CD4(+) and CD8(+) T cells in vitro. Finally, migration of skin DCs was not altered after TNCB application due to Cytip deficiency. Taken together, these data suggest a suppressive function for Cytip in mouse DCs in limiting immune responses.