Journal article
Lung CD4 + resident memory T cells use airway secretory cells to stimulate and regulate onset of allergic airway neutrophilic disease
Cell reports (Cambridge), Vol.44(3), 115294
03/2025
DOI: 10.1016/j.celrep.2025.115294
PMCID: PMC12011213
PMID: 39965565
Abstract
Neutrophilic asthma is a vexing disease, but mechanistic and therapeutic advancements will require better models of allergy-induced airway neutrophilia. Here, we find that periodic ovalbumin (OVA) inhalation in sensitized mice elicits rapid allergic airway inflammation and pathophysiology mimicking neutrophilic asthma. OVA-experienced murine lungs harbor diverse clusters of CD4
resident memory T (T
) cells, including unconventional RORγt
T helper 17 (T
17) cells. Acute OVA challenge instigates interleukin (IL)-17A secretion from these T
cells, driving CXCL5 production from Muc5ac
airway secretory cells, leading to destructive airway neutrophilia. The T
and epithelial cell signals discovered herein are also observed in adult human asthmatic airways. Epithelial antigen presentation regulates this biology by skewing T
cells toward T
2 and T
1 fates so that T
1-related interferon (IFN)-γ suppresses IL-17A-driven, CXCL5-mediated airway neutrophilia. Concordantly, in vivo IFN-γ supplementation improves disease outcomes. Thus, using our model of neutrophilic asthma, we identify lung epithelial-CD4
T
cell crosstalk as a key rheostat of allergic airway neutrophilia.
Details
- Title: Subtitle
- Lung CD4 + resident memory T cells use airway secretory cells to stimulate and regulate onset of allergic airway neutrophilic disease
- Creators
- Vijay Raaj Ravi - University of MichiganFiliz T Korkmaz - University of Massachusetts Chan Medical SchoolCarolina Lyon De Ana - Boston UniversityLu Lu - University of MichiganFeng-Zhi Shao - Boston UniversityChristine V Odom - Boston UniversityKimberly A Barker - Boston UniversityAditya Ramanujan - Boston UniversityEmma N Niszczak - University of MichiganWesley N Goltry - Boston UniversityIan M C Martin - Boston UniversityCatherine T Ha - Boston UniversityLee J Quinton - Boston UniversityMatthew R Jones - Boston UniversityAlan Fine - Boston UniversityJoshua D Welch - University of MichiganFelicia Chen - Boston UniversityAnna C Belkina - Boston UniversityJoseph P Mizgerd - Boston UniversityAnukul T Shenoy - Boston University
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.44(3), 115294
- DOI
- 10.1016/j.celrep.2025.115294
- PMID
- 39965565
- PMCID
- PMC12011213
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Publisher
- CELL PRESS
- Grant note
- NIH: F32 HL147461, K99 HL159258, F31 HL142199, R01 HL136725, R01 HG010883, R01 GM120060, R01 HL111449, R01 AI115053, R35 HL135756, R33 HL137081, K99 HL157555, R00 HL157555, T32 HL007035 Endowment for Basic Science from the University of Michigan
We thank Drs. George O'Connor, Frederic Little, and John Bernardo for helpful discussions. We thank Olivia Harlow and Fang Ke for technical assistance and the Department of Microbiology and Immunology at the University of Michigan for support with flow cytometry. We thank Brian Tilton and the Boston Univer-sity Chobanian & Avedisian School of Medicine Flow Cytometry Core Facility (BU-FCCF) for assistance with FACS. This work was supported by NIH grants, including F32 HL147461 and K99 HL159258 to F.T.K.; F31 HL142199 to K.A.B.; R01 HL136725 to M.R.J. and A.F.; R01 HG010883 to J.D.W.; R01 GM120060 and R01 HL111449 to L.J.Q.; R01 AI115053, R35 HL135756, and R33 HL137081 to J.P.M.; and K99 HL157555 and R00 HL157555 to A.T.S., plus T32 HL007035 for support of trainees. This work was also sup-ported by institutional funding and the Endowment for Basic Science from the University of Michigan to A.T.S.
- Language
- English
- Electronic publication date
- 02/11/2025
- Date published
- 03/2025
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984792367302771
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