2. Academic Validation
  3. Eos Promotes TH2 Differentiation by Interacting with and Propagating the Activity of STAT5

Eos Promotes TH2 Differentiation by Interacting with and Propagating the Activity of STAT5

  • J Immunol. 2023 Aug 1;211(3):365-376. doi: 10.4049/jimmunol.2200861.
Jasmine A Tuazon 1 2 3,  Kaitlin A Read 1 2,  Bharath K Sreekumar 4,  Jack E Roettger 1 2,  Michael J Yaeger 5,  Sanjay Varikuti 5,  Srijana Pokhrel 1,  Devin M Jones 1 2,  Robert T Warren 1,  Michael D Powell 6,  Mustafa N Rasheed 7,  Elizabeth G Duncan 8,  Lauren M Childs 9,  Kymberly M Gowdy 5,  Kenneth J Oestreich 1 10 11
Affiliations

Affiliations

  • 1 Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH.
  • 2 Biomedical Sciences Graduate Program, The Ohio State University College of Medicine, Columbus, OH.
  • 3 Medical Scientist Training Program, The Ohio State University College of Medicine, Columbus, OH.
  • 4 Gladstone Institute of Virology and Immunology, San Francisco, CA.
  • 5 Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH.
  • 6 Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA.
  • 7 Department of Emergency Medicine, Emory University Medical Center, Atlanta, GA.
  • 8 Department of Statistics, Virginia Tech, Blacksburg, VA.
  • 9 Department of Mathematics, Virginia Tech, Blacksburg, VA.
  • 10 Pelotonia Institute for Immuno-Oncology, The Ohio State Comprehensive Cancer Center, Columbus, OH.
  • 11 Infectious Diseases Institute, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH.
PMID: 37314436 DOI: 10.4049/jimmunol.2200861
Abstract

The Ikaros zinc-finger transcription factor Eos has largely been associated with sustaining the immunosuppressive functions of regulatory T cells. Paradoxically, Eos has more recently been implicated in promoting proinflammatory responses in the dysregulated setting of autoimmunity. However, the precise role of Eos in regulating the differentiation and function of effector CD4+ T cell subsets remains unclear. In this study, we find that Eos is a positive regulator of the differentiation of murine CD4+ TH2 cells, an effector population that has been implicated in both immunity against helminthic parasites and the induction of allergic asthma. Using murine in vitro TH2 polarization and an in vivo house dust Mite asthma model, we find that EosKO T cells exhibit reduced expression of key TH2 transcription factors, effector cytokines, and Cytokine Receptors. Mechanistically, we find that the IL-2/STAT5 axis and its downstream TH2 gene targets are one of the most significantly downregulated pathways in Eos-deficient cells. Consistent with these observations, we find that Eos forms, to our knowledge, a novel complex with and supports the tyrosine phosphorylation of STAT5. Collectively, these data define a regulatory mechanism whereby Eos propagates STAT5 activity to facilitate TH2 cell differentiation.

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