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CC BY 4.0 · Semin Respir Crit Care Med
DOI: 10.1055/a-2716-5737
Review Article

Immunopathogenesis of Sarcoidosis

Authors

  • Christen Vagts

    1   Division of Pulmonary Critical Care Sleep and Allergy, Department of Medicine, University of Illinois Chicago, Chicago, Illinois, United States

  • Christian Ascoli

    1   Division of Pulmonary Critical Care Sleep and Allergy, Department of Medicine, University of Illinois Chicago, Chicago, Illinois, United States

  • Jeffrey R. Jacobson

    1   Division of Pulmonary Critical Care Sleep and Allergy, Department of Medicine, University of Illinois Chicago, Chicago, Illinois, United States

Funding Information Funding was provided by the Foundation for Sarcoidosis Fellowship Grant.
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Abstract

Sarcoidosis is a granulomatous disease of unknown cause, triggered by an unidentified antigen. Although classically considered a T cell–mediated disorder with an IFN-γ signature driven by Th1, Th17, and Th17.1 cells, its pathogenesis reflects dysregulated crosstalk between innate and adaptive immunity. Granulomas form through macrophage differentiation at the core, fueled by aberrantly programmed monocytes and sustained by persistent antigen presentation to T cells. Hyperactive macrophages drive excessive peripheral cell recruitment, while dysregulated T cell responses promote T cell expansion, impaired effector regulation, and eventual exhaustion. Deficient regulatory pathways fail to counterbalance this activation, creating a perpetuating inflammatory loop that underlies disease persistence and fibrotic progression. This review integrates up-to-date transcriptomic and biological data to define the cellular and molecular mechanisms that initiate, sustain, and dysregulate immune responses in sarcoidosis.

Keywords

sarcoidosis - immunopathogenesis - granulomatous inflammation - innate immunity - adaptive immunity - interstitial lung disease


Publication History

Received: 15 August 2025

Accepted: 02 October 2025

Article published online:
06 November 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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