Psoriasis is an autoimmune inflammatory
skin disease characterized by activated IL-23/STAT3/Th17 axis. Recently psoriatic
inflammation has been shown to be associated with
asthma. However, no study has previously explored how psoriatic
inflammation affects airway
inflammation. Therefore, this study investigated the effect of
imiquimod (IMQ)-induced psoriatic
inflammation on cockroach extract (CE)-induced airway
inflammation in murine models. Mice were subjected to topical and
intranasal administration of IMQ and CE to develop psoriatic and airway
inflammation respectively. Various analyses in lung/spleen related to
inflammation, Th17/Th2/Th1 cell immune responses, and their signature
cytokines/
transcription factors were carried out. Psoriatic
inflammation in allergic mice was associated with increased airway
inflammation with concurrent increase in Th2/Th17 cells/signature
cytokines/
transcription factors. Splenic CD4+ T and CD11c+ dendritic cells in psoriatic mice had increased STAT3/RORC and
IL-23 mRNA expression respectively. This led us to explore the effect of systemic IL-23/STAT3 signaling on airway
inflammation. Topical application of
STA-21, a small molecule STAT3 inhibitor significantly reduced airway
inflammation in allergic mice having psoriatic
inflammation. On the other hand, adoptive transfer of IL-23-treated splenic CD4+ T cells from allergic mice into naive recipient mice produced mixed neutrophilic/eosinophilic airway
inflammation similar to allergic mice with psoriatic
inflammation. Our data suggest that systemic IL-23/STAT3 axis is responsible for enhanced airway
inflammation during
psoriasis. The current study also suggests that only anti-
asthma therapy may not be sufficient to alleviate airway inflammatory burden in asthmatics with
psoriasis.