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

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Riding, Alexandra M 
Loudon, Kevin W 
Guo, Andrew 
Ferdinand, John R 
Lok, Laurence SC 

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.

Cell biology, Immunology, Transcriptomics
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Elsevier BV
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)