Group 3 innate lymphocytes make a distinct contribution to type 17 immunity in bladder defence

Area of Science:

• Immunology
• Microbiology
• Urology

Background:

• Bladder infections are common, affecting millions globally.
• Current understanding of bladder immunity, particularly type 17 responses, remains incomplete.

Purpose of the Study:

• To investigate the role of type 17 immune responses in the bladder during bacterial infection.
• To identify the cellular sources of key cytokines like IL-17 and IL-22 in bladder immunity.

Main Methods:

• Uropathogenic *Escherichia coli* (UPEC) challenge in mouse models.
• Intravital imaging and gene expression analysis (including *Il17*, *IL22*, *Rorc*).
• Single-cell RNA sequencing and identification of innate lymphoid cell (ILC) subsets.

Main Results:

• Type 17 immune response genes were significantly upregulated in the mouse bladder post-UPEC challenge.
• Group 3 innate lymphoid cells (ILC3s), identified as *Rorc*+ cells, were responsive to UPEC and produced IL-17.
• Both NCR-positive and negative ILC3 subsets were found in murine and human bladders, with increased IL-17 production post-infection.

Conclusions:

• ILC3s are a significant source of IL-17 in the bladder, contributing to type 17 immunity against UPEC.
• While ILC3s contribute to IL-17, Th17 cells are a prominent early source of IL-22.
• The study reveals potential interactions between ILC3s and myeloid cells, offering insights into bladder defense mechanisms.