Novel CD200 homologues iSEC1 and iSEC2 are gastrointestinal secretory cell-specific ligands of inhibitory receptor CD200R.
CD200R is an inhibitory receptor expressed on myeloid cells and some lymphoid cells, and plays important roles in negatively regulating immune responses. CD200 is the only known ligand of CD200R and broadly distributed in a variety of cell types. Here we identified novel CD200 homologues, designated iSEC1 and iSEC2, that are expressed exclusively by secretory cell lineages in the gastrointestinal epithelium while authentic CD200 is expressed by none of epithelial cells including secretory cells. Both iSEC1 and iSEC2 could bind to CD200R but not other members of the CD200R family. Notably, CD200R expression was confined to intraepithelial lymphocytes (IELs) among cells in the gastrointestinal epithelium. Binding of iSEC1 to CD200R on IELs resulted in the suppression of cytokine production and cytolytic activity by activated IELs. Thus, iSEC1 is a previously unappreciated CD200R ligand with restricted expression in gastrointestinal secretory cells and may negatively regulate mucosal immune responses.
Department of Immune Regulation, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Toshiyuki
T
Kojima
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences. Tokyo 113-8519, Japan.
Kiichiro
K
Tsuchiya
Division of Structural Biology, Graduate School of Pharmaceutical Sciences, Kumamoto University. Kumamoto 862-0973, Japan.
Shinji
S
Ikemizu
Department of Immune Regulation, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Soichiro
S
Yoshikawa
Department of Immune Regulation, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Yoshinori
Y
Yamanishi
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences. Tokyo 113-8519, Japan.
Mamoru
M
Watanabe
Department of Immune Regulation, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Hajime
H
Karasuyama
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D019070:Cell Lineage; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000166:cytology / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D015703:Antigens, CD; C492346:CD200 receptor, mouse; D016207:Cytokines; D008024:Ligands; D008562:Membrane Glycoproteins; C042739:antigens, CD200