2. Academic Validation
  3. ILC2-derived CGRP triggers acute inflammation and nociceptive responses in bacterial cystitis

ILC2-derived CGRP triggers acute inflammation and nociceptive responses in bacterial cystitis

  • Cell Rep. 2024 Oct 22;43(10):114859. doi: 10.1016/j.celrep.2024.114859.
Zizhuo Yang 1,  Yaxiao Liu 2,  Yinrui Xiang 1,  Rui Chen 1,  Lipeng Chen 1,  Shuai Wang 1,  Linchen Lv 1,  Maolin Zang 1,  Nan Zhou 1,  Shiyang Li 3,  Benkang Shi 4,  Yan Li 5
Affiliations

Affiliations

  • 1 Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Key Laboratory of Urinary Precision Diagnosis and Treatment in Universities of Shandong, Jinan, Shandong, China.
  • 2 Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Key Laboratory of Urinary Precision Diagnosis and Treatment in Universities of Shandong, Jinan, Shandong, China; Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
  • 3 Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China; Advanced Medical Research Institute, Shandong University, Jinan, Shandong, China. Electronic address: lishiyang@sdu.edu.cn.
  • 4 Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Key Laboratory of Urinary Precision Diagnosis and Treatment in Universities of Shandong, Jinan, Shandong, China; Shenzhen Research Institute of Shandong University, Shenzhen, China. Electronic address: bkang68@sdu.edu.cn.
  • 5 Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Key Laboratory of Urinary Precision Diagnosis and Treatment in Universities of Shandong, Jinan, Shandong, China; Shenzhen Research Institute of Shandong University, Shenzhen, China. Electronic address: yanli@sdu.edu.cn.
PMID: 39412984 DOI: 10.1016/j.celrep.2024.114859
Abstract

Calcitonin gene-related peptide (CGRP), a neuropeptide involved in nociceptor neuronal function, plays a critical role in mediating neuroinflammation and pain. In this study, we find that bladder group 2 innate lymphoid cells (ILC2s) function as primary producers of CGRP in the early phase of Bacterial cystitis, contributing to increased inflammation, altered voiding behavior, and heightened pelvic allodynia. Furthermore, we demonstrate that interleukin (IL)-33, a cytokine secreted by urothelial cells, upregulates CGRP production by ILC2s in the bladder during uropathogenic Escherichia coli (UPEC) Infection. Moreover, our research reveals that monocytes expressing high levels of receptor activity-modifying protein 1 (RAMP1), a CGRP Receptor, mediate the pro-inflammatory effects of CGRP-producing ILC2s. In summary, our results underscore the significance of the immune cell-derived neuropeptides in the pathology of UPEC Infection, suggesting a promising therapeutic approach targeting the IL-33-ILC2-CGRP axis for managing lower urinary tract symptoms in Bacterial cystitis.

Keywords

CP: Immunology; calcitonin gene-related peptide; group 2 innate lymphoid cells; interleukin-33; receptor activity-modifying protein 1; urinary tract infections.

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