Mechanism of Autoimmune Responses Due to Environmental Exposure of Asbestos

Faculty Mentor Information

Dr. Kinta Serve, Idaho State University; and Larisa McOmber, Idaho State University

Presentation Date

7-16-2026

Abstract

Exposure to asbestos has been linked to the development of many autoimmune diseases, including Rheumatoid Arthritis and Lupus Erythematosus. A possible mechanism underlying these responses may be linked to Neutrophil Extracellular Traps (NETs). NETs are web-like structures made up of DNA, proteases, histones, and other inflammatory compounds released by activated neutrophils. NETs are released following nuclear localization of PAD4 (Peptidyl Arginine Deiminase 4), where it citrullinates histones. Citrullination converts positively charged arginine residues into neutrally charged citrulline, causing the DNA to be released from the histones and expelled extracellularly. Others have shown that PAD4 expulsion as part of NETs can also citrullinate host proteins, resulting in neo-antigens associated with autoimmune responses. We hypothesized that Libby amphibole asbestos exposure leads to excess PAD4 and NETs within the lungs, resulting in citrullination of host proteins and subsequent autoimmune responses. To examine this hypothesis, we exposed mice to an environmental dose of Libby amphibole asbestos and examined the lungs at multiple time points post-exposure. Utilizing flow cytometry, immunofluorescence staining, western blotting, and ELISA, we measured increased neutrophil numbers, increased inflammatory cytokines, and PAD4 expression in mice exposed to asbestos fibers compared to saline controls. Future work will confirm NET deployment following asbestos exposure.

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Mechanism of Autoimmune Responses Due to Environmental Exposure of Asbestos

Exposure to asbestos has been linked to the development of many autoimmune diseases, including Rheumatoid Arthritis and Lupus Erythematosus. A possible mechanism underlying these responses may be linked to Neutrophil Extracellular Traps (NETs). NETs are web-like structures made up of DNA, proteases, histones, and other inflammatory compounds released by activated neutrophils. NETs are released following nuclear localization of PAD4 (Peptidyl Arginine Deiminase 4), where it citrullinates histones. Citrullination converts positively charged arginine residues into neutrally charged citrulline, causing the DNA to be released from the histones and expelled extracellularly. Others have shown that PAD4 expulsion as part of NETs can also citrullinate host proteins, resulting in neo-antigens associated with autoimmune responses. We hypothesized that Libby amphibole asbestos exposure leads to excess PAD4 and NETs within the lungs, resulting in citrullination of host proteins and subsequent autoimmune responses. To examine this hypothesis, we exposed mice to an environmental dose of Libby amphibole asbestos and examined the lungs at multiple time points post-exposure. Utilizing flow cytometry, immunofluorescence staining, western blotting, and ELISA, we measured increased neutrophil numbers, increased inflammatory cytokines, and PAD4 expression in mice exposed to asbestos fibers compared to saline controls. Future work will confirm NET deployment following asbestos exposure.