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


Type
Article
Change log
Authors
Riding, Alexandra M 
Loudon, Kevin W 
Guo, Andrew 
Ferdinand, John R 
Lok, Laurence SC 
Abstract

Bladder infection affects a hundred million people annually, but our understanding of bladder immunity is incomplete. We found type 17 immune response genes among the most up-regulated networks in mouse bladder following uropathogenic Escherichia coli (UPEC) challenge. Intravital imaging revealed submucosal Rorc+ cells responsive to UPEC challenge, and we found increased Il17 and IL22 transcripts in wild-type and Rag2 -/- mice, implicating group 3 innate lymphoid cells (ILC3s) as a source of these cytokines. NCR-positive and negative ILC3 subsets were identified in murine and human bladders, with local proliferation increasing IL17-producing ILC3s post infection. ILC3s made a more limited contribution to bladder IL22, with prominent early induction of IL22 evident in Th17 cells. Single-cell RNA sequencing revealed bladder NCR-negative ILC3s as the source of IL17 and identified putative ILC3-myeloid cell interactions, including via lymphotoxin-β-LTBR. Altogether, our data provide important insights into the orchestration and execution of type 17 immunity in bladder defense.

Description
Keywords
Cell biology, Immunology, Transcriptomics
Journal Title
iScience
Conference Name
Journal ISSN
2589-0042
2589-0042
Volume Title
Publisher
Elsevier BV
Sponsorship
Wellcome Trust (200110/Z/15/Z)
Wellcome Trust (220268/Z/20/Z)
Kidney Research UK (TF_013_20171124)
Wellcome Trust (106809/Z/15/Z)
Medical Research Council (MR/N024907/1)
Arthritis Research UK (21777)