2. Academic Validation
  3. From skin to spinal Cord: How IL-17a Drives psoriatic chronic itch

From skin to spinal Cord: How IL-17a Drives psoriatic chronic itch

  • Brain Behav Immun. 2025 Dec 9:132:106218. doi: 10.1016/j.bbi.2025.106218.
Xin Liu 1,  Jian Jiang 2,  Shiying Lin 2,  Wenqiang Ge 3,  Qingxiao Tao 2,  Suwen Liu 2,  Ouyang Zhanmu 3,  Yang Yang 3,  Bao Chai 4,  Jingyu Zhang 1,  Man Li 5,  Hongxiang Chen 6
Affiliations

Affiliations

  • 1 Department of Dermatology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
  • 2 Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  • 3 Tongji Medical College, Key Laboratory of Neurological Diseases of Hubei Province and National Education Ministry, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 4 Department of Dermatology, The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen 518052, China; Department of Dermatology, Shenzhen Nanshan People's Hospital, Shenzhen 518052, China.
  • 5 Tongji Medical College, Key Laboratory of Neurological Diseases of Hubei Province and National Education Ministry, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: [email protected].
  • 6 Department of Dermatology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Institute of Clinical Allergy Research, Wuhan University, Wuhan 430071, China. Electronic address: [email protected].
PMID: 41381012 DOI: 10.1016/j.bbi.2025.106218
Abstract

Interleukin-17a (IL-17A) has been established as a master regulator of inflammatory cascades in psoriasis pathogenesis. Monoclonal antibodies targeting IL-17A have demonstrated significant efficacy in relieving psoriasis-related symptoms, including the rapid alleviation of chronic itching. However, whether IL-17A is involved in chronic psoriatic pruritus and the specific mechanisms of its action remain poorly understood. In this study, we demonstrate that IL-17A significantly exacerbates chronic itch in a murine model of psoriasis. Mechanistically, IL-17A upregulation in psoriatic skin tissues activated the IL-17A receptor (IL-17Ra) in sensory neurons, subsequently promoting the expression of IL-6 in dorsal root ganglion (DRG) neurons. This neuron-derived IL-6 is transported via sensory nerve fibers to the spinal dorsal horn (SDH), where it triggers astrocyte activation and subsequent IL-1β secretion to potentiates chronic itch signaling in psoriasis. Our findings uncover a neuroimmune circuit in which IL-17a-IL-17Ra signaling on sensory neurons mediates the propagation of pruritic signals from peripheral skin to the central nervous system, with spinal IL-6-astrocyte-IL-1β axis serving as an amplifier of psoriatic pruritus.

Keywords

Astrocyte; Chronic itch; IL-17a; Psoriasis; Sensory neuron; Spinal cord.

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