Deficiency of both L-selectin and ICAM-1 exacerbates imiquimod-induced psoriasis-like skin inflammation through increased infiltration of antigen presenting cells

- The role of ICAM-1 and L-selectin in psoriasiform inflammation was studied.
- Psoriasiform skin inflammation was exacerbated in L-selectin/ICAM-1−/− mice.
- Compensatory upregulation of adhesion molecules was induced upon inflammation.
- Excess deletion of adhesion molecule could exacerbate psoriasiform inflammation.

To assess the role of inter-cellular adhesion molecule (ICAM)-1 and L-selectin in psoriasis pathogenic process, we examined the psoriasiform skin inflammation triggered by imiquimod, a toll-like receptor 7/8 agonist, in mice lacking ICAM-1 (ICAM-1−/−), L-selectin (L-selectin−/−), or both (L-selectin/ICAM-1−/−). Disease severity was significantly reduced in ICAM-1−/− and L-selectin−/− mice compared with wild type mice, while it was exacerbated in L-selectin/ICAM-1−/− mice. Cutaneous interleukin (IL)-17A, IL-23, and tumor necrosis factor (TNF)-α expression was increased in L-selectin/ICAM-1−/− mice compared with wild type mice. Furthermore, only L-selectin/ICAM-1−/− mice was refractory to anti-TNF-α antibody treatment. The skin lesion from L-selectin/ICAM-1−/− mice showed augmented E-selectin expression compared with ICAM-1−/− and L-selectin−/− mice, and augmented E-selectin ligand-1 expression compared with wild type mice. The current study demonstrates that although ICAM-1 and L-selectin regulate psoriasiform inflammation, deleting both L-selectin and ICAM-1 simultaneously would rather induce refractory skin inflammation, due to compensatory up-regulation of other adhesion molecules.