CCR4 and CCR10 ligands play additive roles in mouse contact hypersensitivity.
Psoriasis, atopic dermatitis and allergic contact dermatitis are T-cell-mediated inflammatory skin diseases; chemokine receptors (CCR) 4 and 10 play an important role in the ligand-mediated recruitment of T cells into the skin in mice and humans, specifically with regards to tethering, firm adhesion and subsequent extravasation to the sight of injury. We utilized established murine models of dinitrofluorobenzene-, trimellitic acid anhydride- or oxazalone-induced contact hypersensitivity, to reflect the various Th-polarizations of different skin diseases, and investigated the functional effect of antibody blocking of single CCR ligands or combination therapy to block all CCR4 and CCR10 ligands. Our results indicate a greater reduction in inflammatory response--measured by oedema formation, myeloid cell and neutrophil infiltration and activity and CD3+ cell infiltration at the site of injury--with combination antibody therapy to CCR4 and CCR10 ligands versus controls, in nearly every tested condition. We conclude that blocking CCR4 and CCR10 simultaneously, or their ligands, should be beneficial in the treatment of T-cell-mediated skin diseases.
Mirshahpanah
Parham
P
TRG Inflammation & Immunology, Bayer Schering Pharma AG, Berlin, Germany.
Li
Yi-Yang Yvonne
YY
Burkhardt
Nicole
N
Asadullah
Khusru
K
Zollner
Thomas M
TM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D003877:Dermatitis, Contact / Q000188:drug therapy / Q000503:physiopathology*; D004139:Dinitrofluorobenzene; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy / Q000503:physiopathology; D006098:Granulocytes / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000473:pathology; D010796:Phthalic Anhydrides; D011897:Random Allocation; D054447:Receptors, CCR10 / Q000187:drug effects / Q000502:physiology*; D054398:Receptors, CCR4 / Q000187:drug effects / Q000502:physiology*; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology
D000911:Antibodies, Monoclonal; C515707:Ccr10 protein, mouse; C515355:Ccr4 protein, mouse; D010796:Phthalic Anhydrides; D054447:Receptors, CCR10; D054398:Receptors, CCR4; C015559:trimellitic anhydride; D004139:Dinitrofluorobenzene