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ResearchIn-Press PreviewClinical ResearchEndocrinology Open Access | 10.1172/jci.insight.201704

IFNG-producing self-reactive CD4+ T cells induce autoimmune adrenalitis in a mouse model of Addison’s disease

Arina Andreyeva,1 Juraj Michalik,1 Veronika Niederlova,1 Veronika Cimermanova,1 Ales Drobek,1 Radislav Sedlacek,2 Jan Prochazka,2 Juraj Labaj,2 Olha Fedosieieva,2 Waldemar Kanczkowski,3 Peter Draber,4 André Sulen,5 Ondrej Stepanek,1 and Aleš Neuwirth1

1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

2Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Disease, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

3Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

4Department of Immunobiology, University of Lausanne, Epalinges, Switzerland

5Department of Clinical Science, University of Bergen, Bergen, Norway

Find articles by Andreyeva, A. in: PubMed | Google Scholar

1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

2Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Disease, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

3Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

4Department of Immunobiology, University of Lausanne, Epalinges, Switzerland

5Department of Clinical Science, University of Bergen, Bergen, Norway

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1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

2Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Disease, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

3Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

4Department of Immunobiology, University of Lausanne, Epalinges, Switzerland

5Department of Clinical Science, University of Bergen, Bergen, Norway

Find articles by Niederlova, V. in: PubMed | Google Scholar

1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

2Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Disease, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

3Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

4Department of Immunobiology, University of Lausanne, Epalinges, Switzerland

5Department of Clinical Science, University of Bergen, Bergen, Norway

Find articles by Cimermanova, V. in: PubMed | Google Scholar

1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

2Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Disease, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

3Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

4Department of Immunobiology, University of Lausanne, Epalinges, Switzerland

5Department of Clinical Science, University of Bergen, Bergen, Norway

Find articles by Drobek, A. in: PubMed | Google Scholar

1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

2Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Disease, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

3Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

4Department of Immunobiology, University of Lausanne, Epalinges, Switzerland

5Department of Clinical Science, University of Bergen, Bergen, Norway

Find articles by Sedlacek, R. in: PubMed | Google Scholar

1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

2Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Disease, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

3Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

4Department of Immunobiology, University of Lausanne, Epalinges, Switzerland

5Department of Clinical Science, University of Bergen, Bergen, Norway

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

1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

2Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Disease, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

3Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

4Department of Immunobiology, University of Lausanne, Epalinges, Switzerland

5Department of Clinical Science, University of Bergen, Bergen, Norway

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

1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

2Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Disease, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

3Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

4Department of Immunobiology, University of Lausanne, Epalinges, Switzerland

5Department of Clinical Science, University of Bergen, Bergen, Norway

Find articles by Fedosieieva, O. in: PubMed | Google Scholar

1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

2Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Disease, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

3Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

4Department of Immunobiology, University of Lausanne, Epalinges, Switzerland

5Department of Clinical Science, University of Bergen, Bergen, Norway

Find articles by Kanczkowski, W. in: PubMed | Google Scholar

1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

2Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Disease, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

3Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

4Department of Immunobiology, University of Lausanne, Epalinges, Switzerland

5Department of Clinical Science, University of Bergen, Bergen, Norway

Find articles by Draber, P. in: PubMed | Google Scholar

1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

2Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Disease, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

3Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

4Department of Immunobiology, University of Lausanne, Epalinges, Switzerland

5Department of Clinical Science, University of Bergen, Bergen, Norway

Find articles by Sulen, A. in: PubMed | Google Scholar

1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

2Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Disease, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

3Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

4Department of Immunobiology, University of Lausanne, Epalinges, Switzerland

5Department of Clinical Science, University of Bergen, Bergen, Norway

Find articles by Stepanek, O. in: PubMed | Google Scholar

1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

2Czech Centre for Phenogenomics & Laboratory of Transgenic Models of Disease, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

3Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

4Department of Immunobiology, University of Lausanne, Epalinges, Switzerland

5Department of Clinical Science, University of Bergen, Bergen, Norway

Find articles by Neuwirth, A. in: PubMed | Google Scholar |

Published August 4, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.201704.
Copyright © 2026, Andreyeva 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 August 4, 2026 - Version history
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Abstract

Autoimmune Addison’s disease (AD) is a rare but life-threatening disorder caused by immune-mediated destruction of the adrenal cortex, and progress in therapy has been limited by insufficient mechanistic insight. Here, we establish a model of Experimental Autoimmune Adrenalitis (EAA) that recapitulates key features of AD and reveals sex-dependent differences in disease manifestation within the model. Immunization with peptides derived from the adrenal self-antigen CYP11A1 induces corticosterone insufficiency. We show that autoimmune adrenalitis is driven by IFNG produced by self-reactive CD4+ T cells, promoting granulomatous inflammation in the adrenal cortex. Together, these findings identify IFNG as a central effector of autoimmune adrenalitis and suggest that targeting the IFNG pathway may represent a potential therapeutic strategy for AD.

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  • Version 1 (August 4, 2026): In-Press Preview
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