ILC2-derived CGRP triggers acute inflammation and nociceptive responses in bacterial cystitis
Zizhuo Yang,
Yaxiao Liu,
Yinrui Xiang,
Rui Chen,
Lipeng Chen,
Shuai Wang,
Linchen Lv,
Maolin Zang,
Nan Zhou,
Shiyang Li,
Benkang Shi,
Yan Li
Affiliations
Zizhuo Yang
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
Yaxiao Liu
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
Yinrui Xiang
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
Rui Chen
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
Lipeng Chen
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
Shuai Wang
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
Linchen Lv
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
Maolin Zang
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
Nan Zhou
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
Shiyang Li
Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China; Advanced Medical Research Institute, Shandong University, Jinan, Shandong, China; Corresponding author
Benkang Shi
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; Corresponding author
Yan Li
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; Corresponding author
Summary: 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.
