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A dominant-negative IFNGR1 variant reveals broad immune cell sequestering of IFN-γ
Samantha Chan, … , Vanessa L. Bryant, Lauren J. Howson
Samantha Chan, … , Vanessa L. Bryant, Lauren J. Howson
Published April 15, 2025
Citation Information: J Clin Invest. 2025;135(8):e186799. https://doi.org/10.1172/JCI186799.
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Research Letter Genetics Immunology Article has an altmetric score of 6

A dominant-negative IFNGR1 variant reveals broad immune cell sequestering of IFN-γ

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Abstract

Authors

Samantha Chan, Mai B. Margetts, Longfei Wang, Jack Godsell, Josh Chatelier, Belinda Liu, Charlotte A. Slade, Andrew Brett, Kasha P. Singh, Vanessa L. Bryant, Lauren J. Howson

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Figure 1

IFN-γR1 is ubiquitously overexpressed and sequesters IFN-γ on the surface of patients’ cells.

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IFN-γR1 is ubiquitously overexpressed and sequesters IFN-γ on the surfac...
(A) Familial segregation of the IFNGR1 c.817delA (p.I273fs) variant. (B) Expression of IFN-γR1 on PBMC subsets. (C) pSTAT1 staining of PBMCs stimulated with IFN-γ and gated on monocytes. (D) PBMCs were cultured with LPS and a 10-fold dilution series of IFN-γ. (E) RNA-seq of differentially expressed immune genes. Surface IFN-γ detected on (F) monocytes and (G) PBMC subsets following incubation with IFN-γ. (H) IFN-γ dissociation from monocytes over time. The line represents nonlinear regression and the dashed line the dissociation half-life. Error bars represent SD between technical duplicates. HD, healthy donor; MAIT, mucosal-associated invariant T (cell). NS, no stimulation; P, patient.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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