Mirshahpanah Parham, Li Yi-Yang Yvonne, Burkhardt Nicole, Asadullah Khusru, Zollner Thomas M
TRG Inflammation & Immunology, Bayer Schering Pharma AG, Berlin, Germany.
Exp Dermatol. 2008 Jan;17(1):30-4. doi: 10.1111/j.1600-0625.2007.00630.x.
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.
银屑病、特应性皮炎和过敏性接触性皮炎是T细胞介导的炎症性皮肤病；趋化因子受体（CCR）4和10在配体介导的T细胞向小鼠和人类皮肤募集过程中发挥重要作用，特别是在拴系、牢固黏附以及随后向损伤部位外渗方面。我们利用已建立的二硝基氟苯、偏苯三酸酐或恶唑酮诱导的接触性超敏反应小鼠模型，以反映不同皮肤疾病的各种Th极化情况，并研究了抗体阻断单一CCR配体或联合治疗阻断所有CCR4和CCR10配体的功能效果。我们的结果表明，在几乎每种测试条件下，与对照组相比，针对CCR4和CCR10配体的联合抗体治疗在损伤部位通过水肿形成、髓样细胞和中性粒细胞浸润及活性以及CD3 +细胞浸润来衡量的炎症反应降低幅度更大。我们得出结论，同时阻断CCR4和CCR10或其配体，对治疗T细胞介导的皮肤疾病应该是有益的。
