Pan-CC chemokine neutralization restricts splenocyte egress and reduces inflammation in a model of arthritis

The Journal of Immunology : Official Journal of the American Association of Immunologists
Vanessa BuatoisWalter G Ferlin

Abstract

Chemokines are key regulators of leukocyte trafficking and play a crucial role under homeostatic and inflammatory conditions. Because chemokines are involved in multiple pathologies, they represent an attractive class of therapeutic targets. However, because of the redundancy of this system, neutralizing a single chemokine may be insufficient to achieve therapeutic benefit. Our strategy was to use a Fc-fusion recombinant protein form of the poxvirus-derived viral CC chemokine inhibitor protein (vCCI-Fc) that has the ability to specifically bind to multiple CC chemokines and neutralize their activity. In this study, we demonstrate first that, in vivo, vCCI-Fc prevents CC chemokine-dependent migration of macrophages into inflamed tissue of carageenan-challenged mice. We next studied this effect of inhibiting CC chemokine activity in a model more relevant to human disease, collagen-induced arthritis. Mice receiving vCCI-Fc revealed a striking retention of splenocytes, including activated and IFN-gamma-secreting CD4(+) and CD8(+) T cells, that was associated with a concomitant decrease of cells in the draining lymph nodes. These phenomena resulted in a significant decrease in the incidence of disease and a reduction in clinical sco...Continue Reading

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Citations

Jul 5, 2016·Frontiers in Immunology·Pauline BonvinAmanda E I Proudfoot
Aug 1, 2014·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Eileen McNeillKeith M Channon
Nov 2, 2018·Biological & Pharmaceutical Bulletin·Norihito KikuchiHiroto Kawashima
Apr 5, 2020·Journal of Clinical Medicine·Jordan R YaronAlexandra R Lucas

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