Abstract
Psoriasis-specific proteins dysregulated in keratinocytes and involved in the pathophysiological process of psoriasis remains elusive. We report here that epidermal galectin-3 expression is significantly downregulated in lesional skin, but not in non-lesional skin in psoriasis patients, nor in a group of diseases known as psoriasiform dermatitis clinically and histologically similar to psoriasis. The deficiency of epidermal galectin-3 is sufficient to promote development of psoriatic lesions, as evidenced by more severe skin inflammation in galectin-3 knockout (gal3−/−) mice, compared to wild-type mice, after imiquimod treatment, and in skin from gal3−/− mice grafted onto wildtype mice. The development of psoriatic-like lesions is attributable to 1) the spontaneously tuning up of psoriasis signatures in keratinocytes through JNK pathway; and 2) neutrophil accumulation caused by the enhanced leukocyte-recruiting capacity associated with overexpression of S100A7-9 and CXCL-1, 8 in keratinocytes with impaired galectin-3 expression. Psoriasis-like skin inflammation is significantly improved in gal-3−/− mice both by inhibition of neutrophils accumulation with a selective CXCR2 antagonist of SB225002, and by intracutaneous injection of recombinant galectin-3. Overall, these findings offer promising galectin-3-related diagnostic and therapeutic resolutions of psoriasis.
Original language | English (US) |
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Pages (from-to) | 30-40 |
Number of pages | 11 |
Journal | Journal of Autoimmunity |
Volume | 89 |
DOIs | |
State | Published - May 1 2018 |
Externally published | Yes |
Keywords
- Galectin-3
- Keratinocyte
- Neutrophil
- Pathogenesis
- Psoriasis
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology