Calcium/calmodulin-dependent protein kinase IV promotes imiquimod-induced psoriatic inflammation via macrophages and keratinocytes in mice.
Liang YongYafen YuBao LiHuiyao GeQi ZhenYiwen MaoYanxia YuLu CaoRuixue ZhangZhuo LiYirui WangWencheng FanChang ZhangDaiyue WangSihan LuoYuanming BaiShirui ChenWeiwei ChenMiao LiuJijia ShenLiangdan SunPublished in: Nature communications (2022)
CaMK4 has an important function in autoimmune diseases, and the contribution of CaMK4 in psoriasis remains obscure. Here, we show that CaMK4 expression is significantly increased in psoriatic lesional skin from psoriasis patients compared to healthy human skin as well as inflamed skin from an imiquimod (IMQ)-induced mouse model of psoriasis compared to healthy mouse skin. Camk4-deficient (Camk4 -/- ) mice treated with IMQ exhibit reduced severity of psoriasis compared to wild-type (WT) mice. There are more macrophages and fewer IL-17A + γδ TCR + cells in the skin of IMQ-treated Camk4 -/- mice compared to IMQ-treated WT mice. CaMK4 inhibits IL-10 production by macrophages, thus allowing excessive psoriatic inflammation. Deletion of Camk4 in macrophages alleviates IMQ-induced psoriatic inflammation in mice. In keratinocytes, CaMK4 inhibits apoptosis as well as promotes cell proliferation and the expression of pro-inflammatory genes such as S100A8 and CAMP. Taken together, these data indicate that CaMK4 regulates IMQ-induced psoriasis by sustaining inflammation and provides a potential target for psoriasis treatment.
Keyphrases
- wild type
- oxidative stress
- high fat diet induced
- diabetic rats
- rheumatoid arthritis
- high glucose
- cell proliferation
- mouse model
- protein kinase
- wound healing
- poor prognosis
- newly diagnosed
- ankylosing spondylitis
- disease activity
- soft tissue
- gene expression
- endoplasmic reticulum stress
- cell death
- ejection fraction
- metabolic syndrome
- adipose tissue
- transcription factor
- immune response
- long non coding rna
- body mass index
- combination therapy
- human health