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BibTex format

@article{Sakamachi:2026:10.1126/scitranslmed.adw1028,
author = {Sakamachi, Y and Wiley, E and Trempus, CS and Jacobs, H and Solis, A and Johnson, CG and Meng, X and Hussain, S and Roselli, A and Lipinski, JH and O'Dwyer, DN and Randall, TA and Malphurs, J and Papas, B and Wu, BG and Li, Y and Kugler, MC and Mehta, S and Scappini, E and Thomas, SY and Li, J-L and Zhou, L and Karmaus, PW and Lih, FB and Fessler, MB and McGrath, JA and Gibson, K and Kass, DJ and Gleiberman, A and Andrianova, E and Walts, A and Invernizzi, R and Molyneaux, PL and Yang, IV and Zhang, Y and Kaminski, N and Segal, LN and Schwartz, DA and Gudkov, AV and Garantziotis, S},
doi = {10.1126/scitranslmed.adw1028},
journal = {Sci Transl Med},
title = {Toll-like receptor 5 protects against murine lung fibrosis through reduced dysbiosis, and TLR5 deficiency is associated with human IPF.},
url = {http://dx.doi.org/10.1126/scitranslmed.adw1028},
volume = {18},
year = {2026}
}
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TY  - JOUR
AB  - Idiopathic pulmonary fibrosis (IPF) is a devastating pulmonary disease with no curative treatment other than lung transplantation that results from maladaptive responses to lung epithelial injury; however, the underlying mechanisms remain unclear, and treatment options are limited. Here, we showed that deficiency in the innate immune receptor toll-like receptor 5 (TLR5) is associated with IPF in humans and with increased susceptibility to bleomycin-induced pulmonary fibrosis in mice and that activation of lung epithelial TLR5 through a synthetic flagellin analog protected mice from experimental fibrosis. Mechanistically, epithelial TLR5 activation induced antimicrobial gene expression and ameliorated lung dysbiosis after injury. In contrast, TLR5 deficiency in mice and patients with IPF was associated with lung dysbiosis. Elimination of the microbiome in mice through administration of antibiotics abolished the protective effect of TLR5, and reconstitution of the microbiome by fecal microbiota transplantation rescued the observed phenotype. In conclusion, these studies revealed that TLR5 protects against pulmonary fibrosis through effects on the lung microbiota, providing insight into therapeutic approaches that may ultimately benefit patients with IPF.
AU  - Sakamachi,Y
AU  - Wiley,E
AU  - Trempus,CS
AU  - Jacobs,H
AU  - Solis,A
AU  - Johnson,CG
AU  - Meng,X
AU  - Hussain,S
AU  - Roselli,A
AU  - Lipinski,JH
AU  - O'Dwyer,DN
AU  - Randall,TA
AU  - Malphurs,J
AU  - Papas,B
AU  - Wu,BG
AU  - Li,Y
AU  - Kugler,MC
AU  - Mehta,S
AU  - Scappini,E
AU  - Thomas,SY
AU  - Li,J-L
AU  - Zhou,L
AU  - Karmaus,PW
AU  - Lih,FB
AU  - Fessler,MB
AU  - McGrath,JA
AU  - Gibson,K
AU  - Kass,DJ
AU  - Gleiberman,A
AU  - Andrianova,E
AU  - Walts,A
AU  - Invernizzi,R
AU  - Molyneaux,PL
AU  - Yang,IV
AU  - Zhang,Y
AU  - Kaminski,N
AU  - Segal,LN
AU  - Schwartz,DA
AU  - Gudkov,AV
AU  - Garantziotis,S
DO  - 10.1126/scitranslmed.adw1028
PY  - 2026///
TI  - Toll-like receptor 5 protects against murine lung fibrosis through reduced dysbiosis, and TLR5 deficiency is associated with human IPF.
T2  - Sci Transl Med
UR  - http://dx.doi.org/10.1126/scitranslmed.adw1028
UR  - https://www.ncbi.nlm.nih.gov/pubmed/42234773
VL  - 18
ER  -
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