Journal article
The Cystic Fibrosis Transmembrane Conductance Receptor Brakes Allergic Airway Inflammation
Immunological reviews, Vol.330(1), e70009
03/2025
DOI: 10.1111/imr.70009
PMCID: PMC11843850
PMID: 39981881
Abstract
Cystic fibrosis (CF) is a common autosomal recessive disease resulting from mutations of the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR). Although severe pulmonary neutrophilic inflammation is a primary pathologic feature of CF, more recent studies reveal a role for type 2 inflammation that is characterized by eosinophilia directed by both the innate and adaptive immune systems through ILC2 and CD4
+
Th2 cells, respectively. We have published that a clear type endotype exists within CF subjects stratified by Th2 inflammation, defined by increased obstructive pulmonary disease and a distinct phenotypic signature of increased allergic disease, infections, and burden of CF complications. Further, we showed an increased risk of death among CF subjects with type 2 inflammatory signatures compared to CF subjects lacking significant type 2 inflammation. The mechanisms of this heightened type 2 inflammatory signature in CF are still being defined, but it is clear that airway epithelial cells from CFTR‐deficient mice have increased expression and release of IL‐33, a key activator of ILC2 and Th2 cells, compared to persons with normal CFTR function. Further, there is strong evidence that CF regulates CD4
+
Th2 function in a cell‐intrinsic fashion. These concepts are explored in this review article.
Details
- Title: Subtitle
- The Cystic Fibrosis Transmembrane Conductance Receptor Brakes Allergic Airway Inflammation
- Creators
- Daniel P. Cook - University of IowaR Stokes Peebles Jr - Vanderbilt University
- Resource Type
- Journal article
- Publication Details
- Immunological reviews, Vol.330(1), e70009
- DOI
- 10.1111/imr.70009
- PMID
- 39981881
- PMCID
- PMC11843850
- NLM abbreviation
- Immunol Rev
- ISSN
- 0105-2896
- eISSN
- 1600-065X
- Publisher
- John Wiley and Sons Inc
- Grant note
- Francis Family FoundationParker B. Francis Foundation: K08 AI 181763, R01 AI 145265, R01 AI 111820 National Institutes of HealthCystic Fibrosis Foundation: 101BX004299 United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service
This work was funded by the Parker B. Francis Foundation (D.P.C.), National Institutes of Health (K08 AI 181763-D.P.C., R01 AI 145265-R.S.P., U19 AI 095227-R.S.P., R01 AI 111820), Cystic Fibrosis Foundation (COOK20L0-D.P.C., COOK24A0-KB-D.P.C.), and the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service (101BX004299-R.S.P.).
- Language
- English
- Date published
- 03/2025
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984792365602771
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