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.
Highlights
Dendritic cells (DCs) play a major role in regulating immune responses in quality and quantity
As DCs are the major cell type in initiating contact hypersensitivity (CHS), we investigated the functional role of cytohesin-interacting protein (Cytip) in DCs in more detail
Because of publications with opposite results regarding the respective role of Langerhans cells (LCs) in skin immunity and especially in CHS [9,10,11], LC numbers in the epidermis were assessed by staining epidermal sheets for major histocompatibility complex (MHC) class II and counting-positive cells (Fig. 1B)
Summary
Dendritic cells (DCs) play a major role in regulating immune responses in quality and quantity. Hofer et al [5] showed that Cytip accumulates at the contact zone between human DCs and T cells, and that activation of CD8+ T cells is diminished when Cytip is silenced in DCs in cocultures with CD8+ T cells. Using a Cytip knockout (KO) mouse, Coppola et al [7] showed that Cytip does not affect the development of the immune system, they found fewer white blood cells and lymphocytes in the LNs. The same group demonstrated that the immune response in a virusinduced tumor model (M-MSV) is reduced in Cytip-deficient mice [7]. The same group demonstrated that the immune response in a virusinduced tumor model (M-MSV) is reduced in Cytip-deficient mice [7] Another Cytip-deficient mouse, published by Watford et al [8], showed no effect in the development of the immune system
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