Figure 5 Macrophage-derived cytokines activate JAK2/STAT3 in keratinocytes, driving inflammation and hyperproliferationIn the pathological microenvironment of psoriasis, local macrophages in the skin can secrete pro-inflammatory factors such as interleukin-6 (IL-6) and IL-8 (CXCL8), which specifically act on keratinocytes and induce the activation of the intracellular JAK2/STAT3 signaling pathway. After this pathway is activated, it can widely upregulate the transcription and expression of downstream molecules: chemokines recruit neutrophils to accumulate at the inflammatory site, and interleukins further amplify the local inflammatory cascade reaction. Keratin 16 (K16) and Keratin 17 (K17) along with B-cell lymphoma 2 (Bcl-2) synergistically promote abnormal proliferation of keratinocytes (Bcl-2 maintains the proliferative phenotype through anti-apoptotic effects), and IL-6 can assist in promoting Th17 cell differentiation. These pathological processes work together to continuously intensify skin inflammation and promote the occurrence and progression of psoriasis. (Created with BioRender.com).