Alleviation of imiquimod-induced psoriasis-like symptoms in Rorα-deficient mouse skin
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초록
Retinoic acid receptor-related orphan receptor α (RORα) playsa vital role in various physiological processes, including metabolism,cancer, circadian rhythm, cerebellar development, andinflammation. Although RORα is expressed in the skin, its rolein skin physiology remains poorly elucidated. Herein, Rorα wasexpressed in the basal and suprabasal layers of the epidermis;however, keratinocyte-specific Rorα deletion did not impact normalepidermal formation. Under pathophysiological conditions,Rorα-deficient mice exhibited alleviated psoriasis-like symptoms,including relatively intact epidermal stratification, reduced keratinocytehyperproliferation, and low-level expression of inflammatorycytokines in keratinocytes. Unexpectedly, the splenic populationof Th17 cells was significantly lower in keratinocytespecificRORα deficient mice than in the control. Additionally,Rorα-deficiency reduced imiquimod-induced activation of nuclearfactor-κB and STAT3 in keratinocytes. Therefore, we expectthat RORα inhibitors act on immune cells and keratinocytes tosuppress the onset and progression of psoriasis.
Abstract
Retinoic acid receptor-related orphan receptor α (RORα) playsa vital role in various physiological processes, including metabolism,cancer, circadian rhythm, cerebellar development, andinflammation. Although RORα is expressed in the skin, its rolein skin physiology remains poorly elucidated. Herein, Rorα wasexpressed in the basal and suprabasal layers of the epidermis;however, keratinocyte-specific Rorα deletion did not impact normalepidermal formation. Under pathophysiological conditions,Rorα-deficient mice exhibited alleviated psoriasis-like symptoms,including relatively intact epidermal stratification, reduced keratinocytehyperproliferation, and low-level expression of inflammatorycytokines in keratinocytes. Unexpectedly, the splenic populationof Th17 cells was significantly lower in keratinocytespecificRORα deficient mice than in the control. Additionally,Rorα-deficiency reduced imiquimod-induced activation of nuclearfactor-κB and STAT3 in keratinocytes. Therefore, we expectthat RORα inhibitors act on immune cells and keratinocytes tosuppress the onset and progression of psoriasis.
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