Breakthrough in bidirectional skin-organ crosstalk unveils novel therapeutic avenues for systemic diseases — international team identifies skin as a central hub for systemic inflammation regulation

For decades, the skin was considered merely a passive barrier against environmental threats. In a groundbreaking review titled “Critical role of skin in pathogenesis: bidirectional crosstalk between skin and multiple organs”, published today in MedComm-Future Medicine, Prof. Ting Li and colleagues at Macau University of Science and Technology overturn this view. They position the skin as an active immune, neuroendocrine interface, a “central command center” that detects stress, dispatches immune commands, and receives metabolic feedback from distant organs.

“Think of the skin as the body’s social media platform—constantly posting updates that go viral in other organs,” explains Prof. Li, corresponding author.

Skin-Brain Connection

Within the skin-brain axis, psychological stress triggers cortisol release, activating cutaneous mast cells to exacerbate atopic dermatitis. Conversely, psoriasis-derived IL-17A disrupts the blood-brain barrier, inducing hippocampal neuroinflammation and depressive behaviors. This mechanistic insight explains the elevated incidence of neuropsychiatric disorders in dermatological patients.

IL-17A: The Double-Edged Messenger

The review spotlights IL-17A as a master regulator of multi-organ crosstalk. Acting like a molecular “telegraph”, elevated IL-17A levels link the skin to the liver, gut, joints, and beyond, driving psoriasis, non-alcoholic fatty liver disease, rheumatoid arthritis, and intestinal inflammation simultaneously. In murine models, neutralizing IL-17A not only clears psoriatic lesions but also reduces hepatic fibrosis and glomerular inflammation. Clinically, anti-IL-17A biologics (e.g., secukinumab) demonstrate systemic benefits yet precise, tissue-targeted delivery is essential, as IL-17A blockade can exacerbate Crohn’s disease. “IL-17A inhibitors aren’t universal fixes. It’s like having different Wi-Fi passwords for each organ, so that we must target the right tissue”, notes Wende Deng, first author.

Toward Precision Medicine

The authors outline actionable strategies for precision care: 1) Risk Stratification: Screen psoriasis patients for cutaneous IL-17A levels and microbiome profiles to predict liver and cardiovascular comorbidities. 2) Early Intervention: Block IL-23/Th17 signaling at disease onset to prevent renal and skeletal complications. 3) Personalized “Skin-Organ Interactomes”: Integrate AI-driven multi-omics to map individual signaling networks and guide therapy.

“Our findings open doors to intercept systemic inflammation at its source—right at the skin,” Prof. Li adds. “By collaborating across dermatology and internal medicine, clinicians can design smart interventions that stop diseases before they spread”.

This landmark review signals a shift from organ-centric treatments toward systemic, network-based therapies. By leveraging organ-on-a-chip and spatial multi-omics technologies, researchers can now decode real-time inter-organ dialogues, offering curative strategies for cancer, autoimmune diseases, and beyond. Thus, the skin is no longer a mere window to disease — it is a strategic target for dismantling systemic inflammation.

See the article:

Critical role of skin in pathogenesis: bidirectional crosstalk between skin and multiple organs

https://doi.org/10.1002/mef2.70020