TNF family molecule LIGHT regulates chemokine CCL27 expression on mouse embryonic stem cell-derived dendritic cells through NF-kappaB activation.
Cytokine LIGHT is a type II transmembrane protein belonging to the TNF family that was originally identified as a weak inducer of apoptosis. It plays a role in inducing maturation of dendritic cells, such as upregulating CD80, CD86 expression on dendritic cells. However, whether LIGHT induces CC chemokine expression in DC and promotes their migration remains unknown. In this study, we found that esDC express CCR7 and CCR10 (the receptor of CCL27) upon the LIGHT stimulation. LIGHT also upregulates CCL27, but not CCL19 and CCL21 expression in esDC. The esDC migration potential has been increased in LIGHT activated DCs compared with control cells. LIGHT activated DCs autocrine CCL27 which regulate their migration as Blockage of CCL27 on esDC using neutralizing antibody reduces migration potential. In signaling study, we identified that LIGHT activated NF-kappaB in esDC and inhibition of NF-kappaB activation by specific inhibitor can partly attenuate the effect of LIGHT in regulation of CCL27 expression. Moreover, Shp-2 is required in LIGHT activated NF-kappaB because Knockdown of Shp-2 affects the NF-kappaB activation induced by LIGHT and consequently influences LIGHT mediated CCL27 expression. TRAF6 is critical in DC maturation in recent reports; however, knockdown of TRAF6 expression using siRNA did not alter CCL27 expression in LIGHT matured DCs. Our study demonstrates that LIGHT stimulation enhances CCL27 expression through activation of NF-kappaB in DCs.
Zou
Gang-Ming
GM
Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975 West Walnut Street, IB545, Indianapolis, IN 46202, United States. gzou1@jhmi.edu
Hu
Wen-Yang
WY
Wu
Wei
W
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054425:Chemokine CCL27; D019742:Chemokines, CC / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D054447:Receptors, CCR10; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000502:physiology*; D000097628:Chemokine Receptor D6
D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054425:Chemokine CCL27; D019742:Chemokines, CC; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; D054447:Receptors, CCR10; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D048029:TNF Receptor-Associated Factor 6; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; C515709:Ackr2 protein, mouse; D000097628:Chemokine Receptor D6; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; C119538:Ccl27a protein, mouse; C515707:Ccr10 protein, mouse; C515371:Ccr7 protein, mouse; C505915:Tnfsf14 protein, mouse; C516725:Ptpn11 protein, mouse