Publication Type
Journal Article
Version
publishedVersion
Publication Date
9-2024
Abstract
Sarcoidosis is a multiorgan granulomatous disease that lacks diagnostic biomarkers and targeted treatments. Using blood and skin from patients with sarcoid and non-sarcoid skin granulomas, we discovered that skin granulomas from different diseases exhibit unique immune cell recruitment and molecular signatures. Sarcoid skin granulomas were specifically enriched for type 1 innate lymphoid cells (ILC1s) and B cells and exhibited molecular programs associated with formation of mature tertiary lymphoid structures (TLSs), including increased CXCL12/CXCR4 signaling. Lung sarcoidosis granulomas also displayed similar immune cell recruitment. Thus, granuloma formation was not a generic molecular response. In addition to tissue-specific effects, patients with sarcoidosis exhibited an 8-fold increase in circulating ILC1s, which correlated with treatment status. Multiple immune cell types induced CXCL12/CXCR4 signaling in sarcoidosis, including Th1 T cells, macrophages, and ILCs. Mechanistically, CXCR4 inhibition reduced sarcoidosis-activated immune cell migration, and targeting CXCR4 or total ILCs attenuated granuloma formation in a noninfectious mouse model. Taken together, our results show that ILC1s are a tissue and circulating biomarker that distinguishes sarcoidosis from other skin granulomatous diseases. Repurposing existing CXCR4 inhibitors may offer a new targeted treatment for this devastating disease.
Keywords
Cellular immune response, Dermatology, Immunology, Innate immunity
Discipline
Econometrics
Research Areas
Econometrics
Publication
The Journal of Clinical Investigation
Volume
134
Issue
17
First Page
1
Last Page
18
ISSN
0021-9738
Identifier
10.1172/JCI178711
Publisher
American Society for Clinical Investigation
Citation
SATI, Satish; HUANG, Jianhe; KERSH, Anna E.; JONES, Parker; AHART, Olivia; MURPHY, Christina; PROUTY, Stephen M.; HEDBERG, Matthew L.; JAIN, Vaibhav; GREGORY, Simon G.; LEUNG, Denis H. Y.; SEYKORA, John T.; ROSENBACH, Misha; and LEUNG, Thomas H..
Recruitment of CXCR4+ type 1 innate lymphoid cells distinguishes sarcoidosis from other skin granulomatous diseases. (2024). The Journal of Clinical Investigation. 134, (17), 1-18.
Available at: https://ink.library.smu.edu.sg/soe_research/2881
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Additional URL
https://doi.org/10.1172/jci178711