- DETC have been characterized phenotypically by the expression of T cell receptors and functionally by in vivo immunosuppressive activities. The principal investigator has observed that DETC secrete biologically relevant amounts of IL-13 which inhibits the production of proinflammatory cytokines by both keratinocytes and Langerhans cell lines. Very little information is available regarding the function of IL-13 in skin, and the principal investigator proposes to study the biology of this cytokine. Their hypothesis is that IL-13 production by DETC silences immunologic response of neighboring keratinocytes and LC to proinflammatory stimuli, suppressing subsequent immune reactions. They suggest that there is a costimulatory role for LC in supporting IL-13 secretion. They have cloned two glycoproteins called dectin-1 and -2 that are expressed by LCs, and recombinant dectin-1 binds to the surface of DETC. Also Langerhans cell-dependent IL-13 secretion is blocked by anti-dectin-2 monoclonal antibodies. There are five specific aims. 1) They wish to identify in vitro effects of IL-13 on immunologic properties of keratinocytes and LCs. Epidermal cells will be cultured in the presence of IL-13 and examined for changes in cytokine production, surface phenotype, mitotic potential, and antigen presentation. 2) They wish to determine the in vivo impact of IL-13 when overproduced locally. They will target IL-13 gene expression in DETC in mouse skin by delivery by a gene gun of a IL-13 cDNA under control of the TCR -chain promoter. 3) They will test the extent to which IL-13 accounts for immunosuppressive activities, by sensitization of mice through skin sites where recombinant IL-13 is injected locally or overproduced by DETC. 4) They wish to characterize the dectin ligands expressed on DETC by mammalian cell expression cloning using his-dectin-1 as a probe. 5) They wish to study mechanisms that may regulate IL-13 production in DETC by examining environmental stimuli as opposed to internal stimuli. Through these five specific aims they intend to uncover unique activities of IL-13 in the skin.
| Matsushima, Hironori; Takashima, Akira (2010) Bidirectional homing of Tregs between the skin and lymph nodes. J Clin Invest 120:653-6 |
| Matsushima, Hironori; Ogawa, Yasushi; Miyazaki, Toru et al. (2010) Intravital imaging of IL-1beta production in skin. J Invest Dermatol 130:1571-80 |
| Mayuzumi, Nobuyasu; Matsushima, Hironori; Takashima, Akira (2009) IL-33 promotes DC development in BM culture by triggering GM-CSF production. Eur J Immunol 39:3331-42 |
| Matsushima, Hironori; Tanaka, Hiroaki; Mizumoto, Norikatsu et al. (2009) Identification of crassin acetate as a new immunosuppressant triggering heme oxygenase-1 expression in dendritic cells. Blood 114:64-73 |
| Mizumoto, Norikatsu; Tanaka, Hiroaki; Matsushima, Hironori et al. (2007) Colchicine promotes antigen cross-presentation by murine dendritic cells. J Invest Dermatol 127:1543-6 |
| Ward, Brant R; Jester, James V; Nishibu, Akiko et al. (2007) Local thermal injury elicits immediate dynamic behavioural responses by corneal Langerhans cells. Immunology 120:556-72 |
| Ogawa, Yasushi; Mizumoto, Norikatsu; Tanaka, Hiroaki et al. (2006) Identification of novel pharmacological activities of an antifungal agent, nystatin, to promote dendritic cell maturation. J Invest Dermatol 126:349-53 |
| Mizumoto, Norikatsu; Hui, Francis; Edelbaum, Dale et al. (2005) Differential activation profiles of multiple transcription factors during dendritic cell maturation. J Invest Dermatol 124:718-24 |
| Mizumoto, Norikatsu; Gao, Jimin; Matsushima, Hironori et al. (2005) Discovery of novel immunostimulants by dendritic-cell-based functional screening. Blood 106:3082-9 |
| Matsue, Hiroyuki; Matsue, Keiko; Edelbaum, Dale et al. (2004) New strategy for efficient selection of dendritic cell-tumor hybrids and clonal heterogeneity of resulting hybrids. Cancer Biol Ther 3:1145-51 |
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