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ResearchIn-Press PreviewImmunologyInfectious disease Open Access | 10.1172/jci.insight.180287

Aiolos promotes CXCR3 expression on TH1 cells via positive regulation of IFNγ/STAT1 signaling

Melissa R. Leonard,1 Devin M. Jones,1 Kaitlin A. Read,1 Srijana Pokhrel,1 Jasmine A. Tuazon,1 Robert T. Warren,1 Jacob S. Yount,1 and Kenneth J. Oestreich1

1Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, United States of America

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1Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, United States of America

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1Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, United States of America

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1Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, United States of America

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1Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, United States of America

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1Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, United States of America

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1Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, United States of America

Find articles by Yount, J. in: JCI | PubMed | Google Scholar

1Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, United States of America

Find articles by Oestreich, K. in: JCI | PubMed | Google Scholar

Published November 19, 2024 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.180287.
Copyright © 2024, Leonard et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published November 19, 2024 - Version history
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Abstract

CD4+ T helper 1 (TH1) cells coordinate adaptive immune responses to intracellular pathogens, including viruses. Key to this function is the ability of TH1 cells to migrate within secondary lymphoid tissues, as well as to sites of inflammation, which relies on signals received through the chemokine receptor CXCR3. CXCR3 expression is driven by the TH1 lineage-defining transcription factor T-bet, and the cytokine-responsive Signal Transducer and Activator of Transcription (STAT) family members STAT1 and STAT4. Here, we identify the Ikaros zinc finger (IkZF) transcription factor Aiolos (Ikzf3) as an additional positive regulator of CXCR3 both in vitro and in vivo using a murine model of influenza virus infection. Mechanistically, we find that Aiolos-deficient CD4+ T cells exhibit decreased expression of key components of the IFNγ/STAT1 signaling pathway, including JAK2 and STAT1. Consequently, Aiolos deficiency results in decreased levels of STAT1 tyrosine phosphorylation and reduced STAT1 enrichment at the Cxcr3 promoter. We further find that Aiolos and STAT1 form a positive feedback loop via reciprocal regulation of each other downstream of IFNγ signaling. Collectively, our study demonstrates that Aiolos promotes CXCR3 expression on TH1 cells by propagating the IFNγ/STAT1 cytokine signaling pathway.

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  • Version 1 (November 19, 2024): In-Press Preview
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