Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 regulates the induction of Langerhans cell maturation
✍ Scribed by Atsushi Fukunaga; Hiroshi Nagai; Xijun Yu; Shuntaro Oniki; Hideki Okazawa; Sei-ichiro Motegi; Ryuji Suzuki; Nakayuki Honma; Takashi Matozaki; Chikako Nishigori; Tatsuya Horikawa
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 394 KB
- Volume
- 36
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
Recently, we reported that Src homology 2 domain‐containing protein tyrosine phosphatase substrate 1 (SHPS‐1) plays an important role in the migration of Langerhans cells (LC). Here, we show that SHPS‐1 is involved in the maturation of LC. Immunofluorescence analysis on epidermal sheets for I‐A or CD86 revealed that LC maturation induced by 2,4‐dinitro‐1‐fluorobenzene (DNFB) or by TNF__‐__α was inhibited by pretreatment with an anti‐SHPS‐1 monoclonal antibody (mAb) or with CD47‐Fc fusion protein, a ligand for SHPS‐1. Further, FACS analysis demonstrated that I‐A^+^ LC that had emigrated from skin explants expressed CD80 or CD86, whereas CD47‐Fc protein reduced CD80^high+^ or CD86^high+^ cells. CD47‐Fc protein also reduced the up‐regulation of surface CD80 or CD86 by LC remaining in the skin explants. In SHPS‐1 mutant mice, we observed that the up‐regulation of surface CD86 and CCR7 by LC induced by DNFB as well as that of surface CD80 and CD86 by LC in skin explants was attenuated. Finally, contact hypersensitivity (CHS) response was suppressed in SHPS‐1 mutant mice and in wild‐type mice treated with an anti‐SHPS‐1 mAb. These observations indicate that SHPS‐1 plays an important role in the maturation of LC ex vivo and in vivo, and that SHPS‐1‐CD47 interaction may negatively regulate CHS.