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
  • 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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