Paired Ig-Like Type 2 Receptor-Derived Agonist Ligands Ameliorate Inflammatory Reactions by Downregulating β1 Integrin Activity.
The paired immunoglobulin-like type 2 receptor (PILR) family consists of two functionally opposite members, inhibitory PILRα and activating PILRβ receptors. PILRs are widely expressed in various immune cells and interact with their ligands, especially CD99 expressed on activated T cells, to participate in immune responses. Here we investigated whether PILR-derived agonists inhibit β1 integrin activity as ligands for CD99. PILR-derived peptides as well as PILR-Fc fusion proteins prevented cell adhesion to fibronectin through the regulation of β1 integrin activity. Especially, PILRpep3, a representative 3-mer peptide covering the conserved motifs of the PILR extracellular domain, prevented the clustering and activation of β1 integrin by dephosphorylating FAK and vinculin, which are major components of focal adhesion. In addition, PILRpep3 inhibited transendothelial migration of monocytes as well as endothelial cell tube formation. Furthermore, upon intraperitoneal injection of PILRpep3 into mice with collagen-induced arthritis, the inflammatory response of rheumatoid arthritis was strongly suppressed. Taken together, these results suggest that PILR-derived agonist ligands may prevent the inflammatory reactions of rheumatoid arthritis by activating CD99.
Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
Kyoung-Jin
KJ
Lee
Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
Dongyoung
D
Lim
Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
Yeon Ho
YH
Yoo
Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
Eun-Ji
EJ
Park
Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
Sun-Hee
SH
Lee
Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
Birendra Kumar
BK
Yadav
Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
Yong-Ki
YK
Lee
Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
Jeong Hyun
JH
Park
Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
Daejoong
D
Kim
Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
Kyeong Han
KH
Park
Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
Jang-Hee
JH
Hahn
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007274:Injections, Intraperitoneal; D019012:Integrin beta1 / Q000378:metabolism*; D061986:MCF-7 Cells; D051379:Mice; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000819:agonists* / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*
D005353:Fibronectins; D019012:Integrin beta1; D010455:Peptides; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins
CD99; PILR; agonist ligands; inflammation; β1 integrin