Inflammatory signaling pathways in keratinocytes and cytokine expression

Keratinocytes, the predominant cell type in the epidermis, function as active immune sentinels that initiate and amplify skin inflammation. Upon activation by pathogens, allergens, or physical injury, these cells trigger complex intracellular signaling cascades, most notably the Nuclear Factor-kappa B (NF-kappaB), Mitogen-Activated Protein Kinase (MAPK), and Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathways (Pasparakis, J Clin Invest, 2006; Albanesi et al., Front Immunol, 2018). These pathways drive the expression and secretion of a wide array of cytokines and chemokines, including IL-1, IL-6, IL-8, and TNF-alpha, which orchestrate the local inflammatory environment and recruit specialized immune cells like T-cells and neutrophils to the site of injury (Lowes et al., Nat Rev Immunol, 2007). Chronic dysregulation of these signaling networks is a central driver in the pathogenesis of inflammatory dermatoses such as psoriasis and atopic dermatitis, where a feedback loop between keratinocytes and infiltrating immune cells leads to persistent tissue damage and epidermal hyperplasia (Guttman-Yassky et al., J Allergy Clin Immunol, 2020). Modern therapeutic interventions target these pathways by using monoclonal antibodies to neutralize specific cytokines (e.g., TNF, IL-17, IL-23) or small molecules to inhibit the kinases (e.g., JAKs) that propagate the signals. These treatments aim to break the inflammatory cycle, restore skin barrier function, and reduce the clinical symptoms associated with chronic skin inflammation (Nestle et al., NEJM, 2009).

Other names

Keratinocyte inflammatory responseEpidermal cytokine signalingKeratinocyte-mediated inflammationKeratinocyte cytokine network

Inhibition of pro-inflammatory cytokines (e.g., TNF-alpha, IL-17, IL-23), blockade of cytokine receptors (e.g., IL-4R, IL-13R), and inhibition of intracellular signaling transducers such as Janus kinases (JAKs) to prevent the amplification of the inflammatory cascade in the epidermis.