2. Academic Validation
  3. Enhanced interleukin-16-CD4 signaling in CD3 T cell mediates neuropathic pain via activating astrocytes in female mice

Enhanced interleukin-16-CD4 signaling in CD3 T cell mediates neuropathic pain via activating astrocytes in female mice

  • Neuropharmacology. 2024 Nov 15:259:110115. doi: 10.1016/j.neuropharm.2024.110115.
Xuan Zhu 1,  Xiang Li 2,  Siyi Liu 2,  Yun-Han Zhao 2,  Xue-Ru Liu 3,  Xing-Yu Liu 3,  Rongrong Yao 3,  Lixia Tian 3,  Xin-Qi Liu 3,  Fanjun Meng 4,  Lingli Liang 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250013, China; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China; Institute of Neuroscience, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Western China Science and Technology Innovation Harbor, Xi'an, Shaanxi, 710115, China.
  • 2 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China.
  • 3 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China; Institute of Neuroscience, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Western China Science and Technology Innovation Harbor, Xi'an, Shaanxi, 710115, China.
  • 4 Department of Anesthesiology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250013, China. Electronic address: mengliyiyi2000@163.com.
  • 5 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China; Institute of Neuroscience, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Western China Science and Technology Innovation Harbor, Xi'an, Shaanxi, 710115, China. Electronic address: ll2017@xjtu.edu.cn.
PMID: 39137872 DOI: 10.1016/j.neuropharm.2024.110115
Abstract

Immune cells and interleukins play a crucial role in female-specific pain signaling. Interleukin 16 (IL-16) is a cytokine primarily associated with CD4+ T cell function. While previous studies have demonstrated the important role of spinal CD4+ T cells in neuropathic pain, the specific contribution of IL-16 to neuropathic pain remains unclear. In this study, by using a spinal nerve ligation (SNL)-induced neuropathic pain mice model, we found that SNL induced an increase in IL-16 mRNA levels, which persisted for a longer duration in female mice compared to male mice. Immunofluorescence analysis further confirmed enhanced IL-16- and CD4-positive signals in the spinal dorsal horn following SNL surgery in female mice. Knockdown of spinal IL-16 by siRNA or inhibition of CD4 by FGF22-IN-1, a CD4 inhibitor, attenuated established mechanical and thermal pain hypersensitivity induced by SNL. Furthermore, female mice injected with IL-16 intrathecally exhibited significant spontaneous pain, mechanical and thermal hyperalgesia, all of which could be alleviated by FGF22-IN-1 or a CD3 antibody. Additionally, IL-16 induced astrocyte activation but not microglial activation in the spinal dorsal horn of female mice. Meanwhile, astrocyte activation could be suppressed by the CD3 antibody. These results provide compelling evidence that IL-16 promotes astrocyte activation via CD4 on CD3+ T cells, which is critical for maintaining neuropathic pain in female mice.

Keywords

Astrocytes; CD3(+) T cell; CD4; Female; Interleukin-16; Neuropathic pain.

Figures
Products
Inhibitors & Agonists
Other Products