IGF2BP3 promotes NLRC3 translation to regulate macrophage function and alleviate psoriasis

This study aims to investigate the role of insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) in the development of psoriasis, and to explore the underlying molecular mechanisms. To conduct in vivo experiments, we adopted a psoriasis-like mouse model induced by imiquimod (IMQ), while the M5 method was applied to induce HaCaT cells to construct a psoriasis-like cell model. Through in-depth analysis of the ENCORI (Starbase) website, we found that NLR family CARD domain containing 3 (NLRC3) can be effectively combined with IGF2BP3. IGF2BP3 can enhance the translation efficiency and expression level of NLRC3 protein by binding to NLRC3 mRNA. After overexpression (OE) of IGF2BP3, it can inhibit the production of pro-inflammatory factors and cell growth. Animal experiments have also shown that OE-IGF2BP3 can reduce the degree of inflammation and abnormal growth of keratinocytes in psoriasis-like skin lesions. However, sh-NLRC3 has the ability to partially counteract this protective effect. Therefore, IGF2BP3 may exert anti-inflammatory and antiproliferative effects by upregulating NLRC3 expression, positioning it as a promising prognostic biomarker and a novel therapeutic target in psoriasis.