RT Journal Article
T1 IL-17 and TNF-α sustain neutrophil recruitment during inflammation through synergistic effects on endothelial activation.
A1 Griffin, Gabriel
A1 Newton, Gail
A1 Tarri, Margarite
A1 Bu, De-Xiu
A1 Maganto-Garcia, Elena
A1 Azcutia Criado, Verónica
A1 Alcaide, Pilar
A1 Grabie, Nir
A1 Luscinskas, Francis
A1 Croce, Kevin
A1 Lichtman, Andrew
AB IL-17A (IL-17) is the signature cytokine produced by Th17 cells and has been implicated in host defense against infection and the pathophysiology of autoimmunity and cardiovascular disease. Little is known, however, about the influence of IL-17 on endothelial activation and leukocyte influx to sites of inflammation. We hypothesized that IL-17 would induce a distinct pattern of endothelial activation and leukocyte recruitment when compared with the Th1 cytokine IFN-γ. We found that IL-17 alone had minimal activating effects on cultured endothelium, whereas the combination of TNF-α and IL-17 produced a synergistic increase in the expression of both P-selectin and E-selectin. Using intravital microscopy of the mouse cremaster muscle, we found that TNF-α and IL-17 also led to a synergistic increase in E-selectin–dependent leukocyte rolling on microvascular endothelium in vivo. In addition, TNF-α and IL-17 enhanced endothelial expression of the neutrophilic chemokines CXCL1, CXCL2, and CXCL5 and led to a functional increase in leukocyte transmigration in vivo and CXCR2-dependent neutrophil but not T cell transmigration in a parallel-plate flow chamber system. By contrast, endothelial activation with TNF-α and IFN-γ preferentially induced the expression of the integrin ligands ICAM-1 and VCAM-1, as well as the T cell chemokines CXCL9, CXCL10, and CCL5. These effects were further associated with a functional increase in T cell but not neutrophil transmigration under laminar shear flow. Overall, these data show that IL-17 and TNF-α act in a synergistic manner to induce a distinct pattern of endothelial activation that sustains and enhances neutrophil influx to sites of inflammation.
PB The American Association of Immunologists
YR 2012
FD 2012
LK https://hdl.handle.net/20.500.14352/116645
UL https://hdl.handle.net/20.500.14352/116645
LA eng
NO Gabriel K. Griffin, Gail Newton, Margarite L. Tarrio, De-xiu Bu, Elena Maganto-Garcia, Veronica Azcutia, Pilar Alcaide, Nir Grabie, Francis W. Luscinskas, Kevin J. Croce, Andrew H. Lichtman; IL-17 and TNF-α Sustain Neutrophil Recruitment during Inflammation through Synergistic Effects on Endothelial Activation. J Immunol 15 June 2012; 188 (12): 6287–6299. https://doi.org/10.4049/jimmunol.1200385
NO National Institutes of Health
NO Sarnoff Cardiovascular Research Foundation
DS Docta Complutense
RD 10 abr 2025