Critical Role of Neutrophils for the Generation of Psoriasiform Skin Lesions in Flaky Skin Mice

Although T cell dysregulation is thought to underlie the pathogenesis of psoriasis, prominent infiltration and microabscess formation by neutrophils is a distinctive hallmark feature of this common disorder. The exact role of neutrophils in the pathogenesis of psoriasiform alterations in vivo , however, is unknown. Similar to human psoriasis, flaky skin mice ( fsn / fsn ) revealed a prominent infiltrate of neutrophils, and microabscesses within the hyperproliferative epidermis were associated with de novo expression of intercellular adhesion molecule-1. Intraperitoneal injection with the neutrophil-depleting RB6-8C5 monoclonal antibody (anti-Ly-6G) resulted in a dramatic reduction of the epidermal thickness by 58% compared with isotype-treated animals (p  When the integrin α M β 2 (CD11b/CD18), which mediates neutrophil localization through binding to intercellular adhesion molecule-1, was blocked in vivo with the M1/70 monoclonal antibody, the epidermal thickness was reduced by 31% (p  fsn / fsn mice with the MP1-22E9 monoclonal antibody neutralizing granulocyte macrophage-colony stimulating factor, a cytokine stimulating neutrophils by upregulating α M β 2 , resulted in significant reduction of inflammation and acanthosis by 30% (p  fsn / fsn mice, suggesting that blocking neutrophil function may have therapeutic benefit in some human skin disorders.