Aiolos promotes CXCR3 expression by positively regulating IFNγ/STAT1 signaling.

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Presentation Time: 05:00 PM - 05:15 PM
Abstract ID: 4807 - B

Presenting Author:
Melissa R. Leonard , Graduate Research Associate at Ohio State Univ. Col. of Med., Ohio State Univ. Col. of Vet. Med.

Abstract:

CD4⁺ T helper 1 (T_H1) cells coordinate adaptive immune responses to intracellular pathogens such as SARS-CoV-2 and influenza viruses. The ability of T_H1 cells to migrate within secondary lymphoid tissues, as well as to sites of inflammation, relies on signals received through the chemokine receptor CXCR3. CXCR3 expression is driven, in part, by the T_H1 lineage-defining transcription factor, T-bet, and the cytokine responsive Signaling 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 using in vitro T_H1 polarization and an in vivo murine influenza virus infection model. We find that Aiolos-deficient CD4⁺ T cells exhibit decreased expression of key components of the IFNγ/STAT1 signaling pathway, including IFNGR2, JAK2, and STAT1. Consequently, Aiolos deficiency results in reduced levels of STAT1 tyrosine phosphorylation. Mechanistically, we identify Stat1 as a direct Aiolos target gene, as Aiolos both modulates chromatin structure at the Stat1 promoter and directly enhances Stat1 promoter activity. Collectively, our study reveals Aiolos as a multifactorial regulator of the IFNγ/STAT1 signaling pathway in T_H1 cells and a driver of CXCR3 expression.