Journal article
Endothelial cell expression of a STING gain-of-function mutation initiates pulmonary lymphocytic infiltration
Cell reports (Cambridge), Vol.43(4), pp.114114-114114
04/23/2024
DOI: 10.1016/j.celrep.2024.114114
PMCID: PMC11108094
PMID: 38625791
Abstract
Patients afflicted with Stimulator of interferon gene (STING) gain -of -function mutations frequently present with debilitating interstitial lung disease (ILD) that is recapitulated in mice expressing the STING V154M mutation (VM). Prior radiation chimera studies revealed an unexpected and critical role for non-hematopoietic cells in initiating ILD. To identify STING -expressing non-hematopoietic cell types required for the development of ILD, we use a conditional knockin (CKI) model and direct expression of the VM allele to hematopoietic cells, fibroblasts, epithelial cells, or endothelial cells. Only endothelial cell -targeted VM expression results in enhanced recruitment of immune cells to the lung associated with elevated chemokine expression and the formation of bronchus -associated lymphoid tissue, as seen in the parental VM strain. These findings reveal the importance of endothelial cells as instigators of STING -driven lung disease and suggest that therapeutic targeting of STING inhibitors to endothelial cells could potentially mitigate inflammation in the lungs of STING -associated vasculopathy with onset in infancy (SAVI) patients or patients afflicted with other ILD-related disorders.
Details
- Title: Subtitle
- Endothelial cell expression of a STING gain-of-function mutation initiates pulmonary lymphocytic infiltration
- Creators
- Kevin MingJie Gao - University of Massachusetts Chan Medical SchoolKristy Chiang - University of Massachusetts Chan Medical SchoolZhaozhao Jiang - University of Massachusetts Chan Medical SchoolFiliz T. Korkmaz - University of Massachusetts Chan Medical SchoolHarish P. Janardhan - University of Massachusetts Chan Medical SchoolChinmay M. Trivedi - University of Massachusetts Chan Medical SchoolLee J. Quinton - University of Massachusetts Chan Medical SchoolSebastien Gingras - University of PittsburghKatherine A. Fitzgerald - University of Massachusetts Chan Medical SchoolAnn Marshak-Rothstein - University of Massachusetts Chan Medical School
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.43(4), pp.114114-114114
- DOI
- 10.1016/j.celrep.2024.114114
- PMID
- 38625791
- PMCID
- PMC11108094
- NLM abbreviation
- Cell Rep
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Publisher
- Elsevier
- Number of pages
- 27
- Grant note
- R01-HL165787; F30-HL154674; K99-HL159258; R01-HL118100; R01-HL141377; R01-HL165718 / NHLBI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01-A128358; R21-AI178978; T32-AI132152 / NIAID; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) T32-GM107000 / NIGMS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) Lupus Research Alliance Innovation Award
- Language
- English
- Date published
- 04/23/2024
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984696751902771
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