Authors
Irene Dusetti, Gianmarco Conte, Matteo Chiara, Simone Puccio, Daniela Guidone, Eugenia Ricciardelli, Javier Cibella, Mirko Ronzio, Diletta Dolfini, Elio Rossi, Paolo Landini, Miriam Ascagni, Riccardo Orlandi, Francesco Damarco, Alessandro Palleschi, Andrea Gramegna, Francesco Blasi, Enrico Lugli, Luis J Galietta, Søren Molin, Helle K Johansen, Clelia Peano, Moira Paroni
Published in
Nature microbiology. Sep 24, 2026. Epub Sep 24, 2026.
Abstract
Cystic fibrosis (CF) involves cycles of bacterial infection and sustained inflammation. IFNγ+Th17 cells are implicated in chronic inflammation, yet their role in CF remains undefined. Here we identify two pathogenic Th17 subsets, Th1/17+ and pro-inflammatory Th17 (pTh17) cells, selectively enriched in CF lungs colonized by Pseudomonas aeruginosa. These pathogenic subsets derive from protective conventional Th17 (cTh17) precursors and, following activation, directly disrupt pulmonary epithelial integrity and trigger exaggerated inflammatory responses. Transcriptomic and T cell receptor profiling reveal in situ reprogramming and clonal selection of Th1/17+ and pTh17 cells in CF lungs. Mechanistically, clinical P. aeruginosa strains persist within dendritic cells and induce a polarizing IL-1β/IL-23 cytokine axis that promotes IFNγ+Th17 differentiation over classical Th1 lineage commitment. P. aeruginosa early isolates, lacking chronic adaptation signatures, still potently reprogramme cTh17 cells, inducing a transcriptional programme that mirrors CF lung-resident Th1/17+ and pTh17 profiles. These findings show that P. aeruginosa subverts mucosal immunity and establishes a self-sustaining immunopathological loop, offering potential targets for CF precision therapies.
PMID:
42786279
Bibliographic data and abstract were imported from PubMed on 18 Oct 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 16
- Comments 0