tetano
Editor, Senior Moderator
J Exp Med
. 2026 Jan 5;223(1):e20242307.
doi: 10.1084/jem.20242307. Epub 2025 Oct 13. Lung tissue-resident memory T cells optimize protection by IL-10 regulation of innate immunity
Alexander Y Yang[SUP] 1 [/SUP], Julia Davis-Porada[SUP] 1 2 [/SUP], Daniel H Paik[SUP] 2 [/SUP], Alex B George[SUP] 2 3 [/SUP], Brea H Brown[SUP] 1 [/SUP], Paige L Ruschke[SUP] 1 [/SUP], Peter A Sims[SUP] 3 4 [/SUP], Ziv Frankenstein[SUP] 5 [/SUP], Anjali Saqi[SUP] 5 [/SUP], Donna L Farber[SUP] 1 6 [/SUP]
Affiliations
Respiratory viral infections establish tissue-resident memory T cells (TRM) in the lung, which provide optimal protection against subsequent infections, though the underlying mechanisms are incompletely understood. Here, we demonstrate in a mouse model of heterosubtypic influenza infection that lung TRM attenuate inflammation by macrophages during secondary versus primary responses, in part, through production of the immunoregulatory cytokine IL-10. During secondary infections, lung TRM were the predominant producers of early IL-10; inhibiting early IL-10 signaling resulted in increased macrophage-mediated inflammation, morbidity, and lung pathology. Moreover, lung TRM were shown to directly modulate lung macrophage responses and polarization in depletion experiments. Finally, IL-10 enhanced IFN-γ production by lung memory CD8+ T cells. Human influenza-specific TRM isolated from lungs recapitulated robust IL-10 expression associated with augmented effector responses of murine TRM. These data support a dual role of TRM in coordinating in situ secondary responses-augmenting effector responses for robust viral clearance while dampening inflammation to limit tissue damage.
. 2026 Jan 5;223(1):e20242307.
doi: 10.1084/jem.20242307. Epub 2025 Oct 13. Lung tissue-resident memory T cells optimize protection by IL-10 regulation of innate immunity
Alexander Y Yang[SUP] 1 [/SUP], Julia Davis-Porada[SUP] 1 2 [/SUP], Daniel H Paik[SUP] 2 [/SUP], Alex B George[SUP] 2 3 [/SUP], Brea H Brown[SUP] 1 [/SUP], Paige L Ruschke[SUP] 1 [/SUP], Peter A Sims[SUP] 3 4 [/SUP], Ziv Frankenstein[SUP] 5 [/SUP], Anjali Saqi[SUP] 5 [/SUP], Donna L Farber[SUP] 1 6 [/SUP]
Affiliations
- PMID: 41081716
- DOI: 10.1084/jem.20242307
Respiratory viral infections establish tissue-resident memory T cells (TRM) in the lung, which provide optimal protection against subsequent infections, though the underlying mechanisms are incompletely understood. Here, we demonstrate in a mouse model of heterosubtypic influenza infection that lung TRM attenuate inflammation by macrophages during secondary versus primary responses, in part, through production of the immunoregulatory cytokine IL-10. During secondary infections, lung TRM were the predominant producers of early IL-10; inhibiting early IL-10 signaling resulted in increased macrophage-mediated inflammation, morbidity, and lung pathology. Moreover, lung TRM were shown to directly modulate lung macrophage responses and polarization in depletion experiments. Finally, IL-10 enhanced IFN-γ production by lung memory CD8+ T cells. Human influenza-specific TRM isolated from lungs recapitulated robust IL-10 expression associated with augmented effector responses of murine TRM. These data support a dual role of TRM in coordinating in situ secondary responses-augmenting effector responses for robust viral clearance while dampening inflammation to limit tissue damage.