Essential roles of SHPS-1 in induction of contact hypersensitivity of skin.
SHPS-1 is a transmembrane protein that binds the protein tyrosine phosphatases SHP-1 and SHP-2 and is abundant on the surface of CD11c(+) dendritic cells (DCs). We recently showed that SHPS-1 is essential for priming by DCs of CD4(+) T cells and for development of Th17 cell-mediated experimental autoimmunity. We have now further evaluated the importance of SHPS-1 and that of its ligand CD47 in contact hypersensitivity (CHS) to 2,4-dinitro-1-fluorobenzene (DNFB). Whereas the DNFB-induced CHS response was impaired in mice that express a mutant form of SHPS-1 lacking most of the cytoplasmic region, it was unaffected in CD47-deficient mice. Moreover, treatment of wild-type mice with mAbs to SHPS-1 that either block or do not block the binding of SHPS-1 to CD47 inhibited the CHS response. A mAb to CD47 had no such effect. The 2,4-dinitro-benzenesulfonic acid-induced proliferation of, and production of IFN-gamma or IL-17 by, T cells from DNFB-sensitized wild-type mice were inhibited by either mAb to SHPS-1 but not by that to CD47. In contrast, the blocking mAbs to SHPS-1, but not that to CD47, inhibited an allogeneic mixed leukocyte reaction. Both mAbs to SHPS-1, but not that to CD47, also inhibited the lipopolysaccharide- or polyinosinic-polycytidylic acid-induced production of TNF-alpha by DCs. These results suggest that SHPS-1 is essential for development of CHS, likely as a result of its positive regulation of the priming by DCs of CD4(+) T cells. However, such regulation by SHPS-1 does not appear to require its interaction with CD47.
Motegi
Sei-Ichiro
S
Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan.
Okazawa
Hideki
H
Murata
Yoji
Y
Kanazawa
Yoshitake
Y
Saito
Yasuyuki
Y
Kobayashi
Hisae
H
Ohnishi
Hiroshi
H
Oldenborg
Per-Arne
PA
Ishikawa
Osamu
O
Matozaki
Takashi
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D051928:CD47 Antigen / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology* / Q000473:pathology; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D051928:CD47 Antigen; D016207:Cytokines; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D004139:Dinitrofluorobenzene