Interleukin-27 upregulates major histocompatibility complex class II expression in primary human endothelial cells through induction of major histocompatibility complex class II transactivator.
Interleukin-27 (IL-27) is a novel IL-12 family member that plays a critical role in the regulation of T-cell responses. Its immunoregulatory effects on endothelial cells (EC) remain unexplored. Here we show a role for IL-27 in the induction of major histocompatibility complex (MHC) expression in primary human EC. Stimulation of human umbilical vein ECs by IL-27 rapidly induces IFN regulatory factor-1 and dramatically increases the expression of major histocompatibility class II transactivator (CIITA) isoform IV. Expression of this transactivator correlates with increased MHC class II gene expression. IL-27 also enhances expression of MHC class I molecules. Furthermore expression of beta2-microglobulin and transporter associated with antigen processing-1 transcripts increases in response to IL-27. Additional microarray analysis demonstrates that IL-27 significantly upregulates a panel of genes that correlates with immune regulation, including the chemokines CXCL9, CXCL10, and CX3CL1 in human umbilical vein ECs. This first demonstration that both MHC II and I expression are increased in EC after IL-27 stimulation suggests that IL-27 may be important in conferring immune function on vascular endothelium.
Feng
Xiao Ming
XM
State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences, Tianjin, China.
Chen
Xiao Li
XL
Liu
Na
N
Chen
Zhong
Z
Zhou
Yu Ling
YL
Han
Zhi Bo
ZB
Zhang
Lei
L
Han
Zhong Chao
ZC
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000276:immunology / Q000378:metabolism*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000276:immunology / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D018925:Chemokines; D000949:Histocompatibility Antigens Class II; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D020381:Interleukin-17; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; C073119:TAP1 protein, human; D015534:Trans-Activators; D001613:beta 2-Microglobulin