The CRAC channel inhibitor Auxora reprograms pathogenic alveolar macrophage–T cell circuits in viral pneumonia
S. Marina Casalino-Matsuda, Vijeeth Guggilla, Catherine A. Gao, Kaitlyn E. DeMeulenaere, Luisa Cusick, Samuel W. Fenske, Zhan Yu, Ziyan Lu, Suchitra Swaminathan, Rogan A. Grant, Maxwell J. Schleck, Murali Prakriya, Sudarshan Hebbar, Kenneth Stauderman, Helen K. Donnelly, Chiagozie I. Pickens, Luisa Morales-Nebreda, Richard G. Wunderink, Alexander V. Misharin, Benjamin D. Singer, G.R. Scott Budinger
S. Marina Casalino-Matsuda, Vijeeth Guggilla, Catherine A. Gao, Kaitlyn E. DeMeulenaere, Luisa Cusick, Samuel W. Fenske, Zhan Yu, Ziyan Lu, Suchitra Swaminathan, Rogan A. Grant, Maxwell J. Schleck, Murali Prakriya, Sudarshan Hebbar, Kenneth Stauderman, Helen K. Donnelly, Chiagozie I. Pickens, Luisa Morales-Nebreda, Richard G. Wunderink, Alexander V. Misharin, Benjamin D. Singer, G.R. Scott Budinger
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Research Letter Immunology Infectious disease Pulmonology

The CRAC channel inhibitor Auxora reprograms pathogenic alveolar macrophage–T cell circuits in viral pneumonia

Abstract

Authors

S. Marina Casalino-Matsuda, Vijeeth Guggilla, Catherine A. Gao, Kaitlyn E. DeMeulenaere, Luisa Cusick, Samuel W. Fenske, Zhan Yu, Ziyan Lu, Suchitra Swaminathan, Rogan A. Grant, Maxwell J. Schleck, Murali Prakriya, Sudarshan Hebbar, Kenneth Stauderman, Helen K. Donnelly, Chiagozie I. Pickens, Luisa Morales-Nebreda, Richard G. Wunderink, Alexander V. Misharin, Benjamin D. Singer, G.R. Scott Budinger

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Figure 1

Auxora targets T cells to inhibit T cell–macrophage circuits during SARS-CoV-2 pneumonia.

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Auxora targets T cells to inhibit T cell–macrophage circuits during SARS...
(A) Schematic illustrating protocol-driven interventions. (B) Swimmer plots of the ICU course in patients enrolled in the trial. SOFA, sequential organ failure assessment (score assessing viral clearance); ECMO, extracorporeal membrane oxygenation initiated; VAP, ventilator-associated pneumonia episode. (C) Plasma CCL8 and PDGF-AA levels before and after placebo or Auxora infusion. Significance was determined by linear mixed models using a paired design. (D) Schematic for experiments in PBMCs from 5 different blood donors in E–J. (E–J) Genes were identified as differentially expressed by a negative binomial generalized linear model using an ANOVA-like test for differential expression between any conditions in the dataset (FDR q < 0.05). Ax, Auxora. (E) PCA of DEGs in CD4+ T cells. (G) CD8+ T cells (I) MDMs. Heatmaps demonstrating the expression of selected genes of interest among the DEGs in (F) CD4+ T cells, (H) CD8+ T cells, and (J) MDMs.