The schematic figure depicts the pathogenesis of atopic dermatitis (AD). (1) A persistent ‘itch-scratch cycle’ occurs due to the disruption of the essential epidermal proteins such as filaggrin (FLG) and claudin 1 (CLDN1) that results in a compromised epidermal barrier, facilitating allergen penetration (2) into the skin and inflicting damage on keratinocytes (KCs), (3) These damaged KCs release ‘alarmins’, interleukin-25 (IL-25), interleukin-33 (IL-33), and thymic stromal lymphopoietin (TSLP), which (4) activate Th2 cells and innate lymphoid cells (ILC2s) at the site of the inflamed lesion, (5) leading to the production of Th2 cytokines (6) ILCs, primarily ILC2s, secrete interleukin-5 (IL-5) and interleukin-13 (IL-13), (7) with IL-5 subsequently attracting eosinophils. Additionally, (8) TSLP triggers the development of Langerhans cells (LCs) (9) which, in turn, promotes Th2 cell activation. (10 and 11) Th2 cells secrete Th2 cytokines such as interleukin-4 (IL-4) and IL-13 that drive B cells to generate immunoglobulin E (IgE), contributing to hypersensitivity type 1 reaction. (12) Th2 cytokines further stimulate Th2 cells in an autocrine manner. (13 and 14) Upon bacterial infection, most commonly by Staphylococcus aureus, LCs rapidly produce interleukin-23 (IL-23) at the site of infection, (15) thereby activating local Th17/ThIL-17 cells. (16) These cells secrete the Th17 cytokines (17) that are potent chemoattractants for neutrophils. Created in BioRender. Baidya, A. (2024). BioRender.com/d04p354
Declarations
Author contributions
AB: Writing—original draft, Writing—review & editing. UM: Validation, Conceptualization, Writing—original draft, Writing—review & editing, Supervision. Both authors read and approved the submitted version.
Conflicts of interest
The authors declare that they have no conflicts of interest.
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Funding
We would like to acknowledge the funds provided by CSIR [MLP137-MISSION LUNG] and DST SERB [GAP-432]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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