Decoding the Skin Micro-Immune Milieu, Homeostasis, and Keratinocyte Trafficking in Psoriatic Disease

The skin, acting as a complex interface between the immune system and microbiome, maintains balance through coordinated interactions among the epidermal barrier, microbiome, and immune responses. Psoriasis, a chronic autoimmune and inflammatory disorder, disrupts this balance by altering keratinocyte growth, immune signaling, and microbial diversity.

The psoriatic environment exhibits dysbiosis, with reduced α-diversity and increased β-diversity, thereby worsening lesions. Beneficial microbes like Staphylococcus epidermidis provide protection, while opportunistic pathogens such as Staphylococcus aureus, Streptococcus pyogenes, Malassezia, Candida albicans, and HPV can trigger psoriatic outbreaks. Keratinocytes, essential to disease development and progression, interact actively with immune cells, fibroblasts, and Langerhans cells through cytokines, chemokines, and extracellular vesicles, influencing cell movement and inflammation. Changes in pathways like GLUT-1-mediated glucose metabolism and PI3K/Akt/mTOR signaling promote epidermal overgrowth, new blood vessel formation, and immune imbalance. Oxidative stress and mitochondrial dysfunction also weaken skin homeostasis. The skin's lymphoid tissue (SALT) and inducible SALT are crucial for immune surveillance and autoimmunity but become hyperactive in psoriasis.

Understanding the complex network linking the skin microbiome, immune system, and keratinocyte behavior is essential for developing advanced treatments. Combining immunology, molecular biology, and drug delivery science, using molecular docking, in-silico modeling, and nanotherapy, offers promising options for targeted psoriasis therapy.