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Current Sarcoidosis Models and the Importance of Focusing on the Granuloma
Landon W Locke1, Larry S Schlesinger2, Elliott D Crouser3
1Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
Abstract:
The inability to effectively model sarcoidosis in the laboratory or in animals continues to hinder the discovery and translation of new, targeted treatments. The granuloma is the signature pathological hallmark of sarcoidosis, yet there are significant knowledge gaps that exist with regard to how granulomas form. Significant progress toward improved therapeutic and prognostic strategies in sarcoidosis hinges on tractable experimental models that recapitulate the process of granuloma formation in sarcoidosis and allow for mechanistic insights into the molecular events involved. Through its inherent representation of the complex genetics underpinning immune cell dysregulation in sarcoidosis, a recently developed in vitro human granuloma model holds promise in providing detailed mechanistic insight into sarcoidosis-specific disease regulating pathways at play during early stages of granuloma formation. The purpose of this review is to critically evaluate current sarcoidosis models and assess their potential to progress the field toward the goal of improved therapies in this disease. We conclude with the potential integrated use of preclinical models to accelerate progress toward identifying and testing new drugs and drug combinations that can be rapidly brought to clinical trials.
Insights
Developing better laboratory models for sarcoidosis is crucial for discovering new treatments. A new in vitro human granuloma model shows promise for understanding early disease stages and accelerating drug development.
Area of Science:
- Immunology
- Pathology
- Translational Medicine
Background:
- Sarcoidosis treatment discovery is hindered by a lack of effective laboratory and animal models.
- Granuloma formation, the hallmark of sarcoidosis, is not fully understood, creating knowledge gaps.
- Improved models are essential for advancing therapeutic and prognostic strategies for sarcoidosis.
Purpose of the Study:
- To critically evaluate existing sarcoidosis models.
- To assess the potential of current models in advancing sarcoidosis research.
- To identify pathways for developing improved therapies for sarcoidosis.
Main Methods:
- Review of current preclinical sarcoidosis models.
- Evaluation of an in vitro human granuloma model for its ability to recapitulate sarcoidosis.
- Assessment of the model's potential for mechanistic insights into granuloma formation.
Main Results:
- Existing models have limitations in fully recapitulating sarcoidosis.
- The in vitro human granuloma model offers promise for understanding early-stage disease.
- This model can provide mechanistic insights into sarcoidosis-specific pathways.
Conclusions:
- Tractable experimental models are key to advancing sarcoidosis therapeutics.
- The in vitro human granuloma model holds potential for detailed mechanistic studies.
- Integrated use of preclinical models can accelerate drug discovery and clinical trials for sarcoidosis.
