Granzymes, IL-16, and poly(ADP-ribose) polymerase 1 increase during wildfire smoke exposure

Juan Aguilera; Abhinav Kaushik; Nicholas Cauwenberghs; Anja Heider; Ismail Ogulur; Duygu Yazici; Eric Smith; Shifaa Alkotob; Mary Prunicki; Cezmi A Akdis; Kari C Nadeau

doi:10.1016/j.jacig.2023.100093

Granzymes, IL-16, and poly(ADP-ribose) polymerase 1 increase during wildfire smoke exposure

J Allergy Clin Immunol Glob. 2023 May;2(2):100093. doi: 10.1016/j.jacig.2023.100093. Epub 2023 Mar 21.

Authors

Juan Aguilera¹, Abhinav Kaushik², Nicholas Cauwenberghs³, Anja Heider⁴, Ismail Ogulur⁴, Duygu Yazici⁴, Eric Smith⁵, Shifaa Alkotob⁶, Mary Prunicki², Cezmi A Akdis^{4

7}, Kari C Nadeau^{2

8}

Affiliations

¹ the Center for Community Health Impact, University of Texas Health Science Center School of Public Health, El Paso.
² the Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford.
³ the Department of Cardiovascular Sciences, Hypertension and Cardiovascular Epidemiology Research Unit, KU Leuven, Leuven.
⁴ the Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos.
⁵ the David Geffen School of Medicine at University of California, Los Angeles.
⁶ the Indiana University School of Medicine, Indianapolis.
⁷ the Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos.
⁸ the Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston.

Abstract

Background: Given the increasing prevalence of wildfires worldwide, understanding the effects of wildfire air pollutants on human health-particularly in specific immunologic pathways-is crucial. Exposure to air pollutants is associated with cardiorespiratory disease; however, immune and epithelial barrier alterations require further investigation.

Objective: We sought to determine the impact of wildfire smoke exposure on the immune system and epithelial barriers by using proteomics and immune cell phenotyping.

Methods: A San Francisco Bay area cohort (n = 15; age 30 ± 10 years) provided blood samples before (October 2019 to March 2020; air quality index = 37) and during (August 2020; air quality index = 80) a major wildfire. Exposure samples were collected 11 days (range, 10-12 days) after continuous exposure to wildfire smoke. We determined alterations in 506 proteins, including zonulin family peptide (ZFP); immune cell phenotypes by cytometry by time of flight (CyTOF); and their interrelationship using a correlation matrix.

Results: Targeted proteomic analyses (n = 15) revealed a decrease of spondin-2 and an increase of granzymes A, B, and H, killer cell immunoglobulin-like receptor 3DL1, IL-16, nibrin, poly(ADP-ribose) polymerase 1, C1q TNF-related protein, fibroblast growth factor 19, and von Willebrand factor after 11 days' average continuous exposure to smoke from a large wildfire (P < .05). We also observed a large correlation cluster between immune regulation pathways (IL-16, granzymes A, B, and H, and killer cell immunoglobulin-like receptor 3DL1), DNA repair [poly(ADP-ribose) 1, nibrin], and natural killer cells. We did not observe changes in ZFP levels suggesting a change in epithelial barriers. However, ZFP was associated with immune cell phenotypes (naive CD4⁺, T_H2 cells).

Conclusion: We observed functional changes in critical immune cells and their proteins during wildfire smoke exposure. Future studies in larger cohorts or in firefighters exposed to wildfire smoke should further assess immune changes and intervention targets.

Keywords: IL-16; PARP-1; Wildfire exposure; air pollution; granzyme; immune cells; mass cytometry; proteomics; zonulin.

Abstract

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