Within- and cross-tissue gene regulations were disrupted by PM 2.5 nitrate exposure and associated with respiratory functions.

Background: Pathogenesis of complex diseases often involves multiple organs/tissue-types. To date, the PM _2.5 exposure's toxic effects and induced disease risks were not studied at multi-tissue level.
Methods: C57BL/6 mice (n = 40) were exposed to PM _2.5 NO ₃ ^- and clean air, respectively, and afterwards assessed respiratory functions and transcriptome in relevant tissues: blood and lung. We constructed within- and cross-tissue gene regulation networks and identified network modules associated with exposure and respiratory functions.
Results: PM _2.5 NO ₃ ^- exposure elevated naïve B cells proportion in blood (p = 0.0028). Among the 6000 highest expressed genes in blood, 18.8 % (1133 genes) were altered by exposure at p ≤ 0.05 level, among which 763 genes were also associated with respiratory function (enrichment folds = 7.63, p = 2.7E-189). The exposure disrupted blood genes were primarily in the immunoregulation pathways. Both within- and cross-tissue gene network modules were perturbed by exposure and associated with respiratory function. An immunodeficiency related cross-tissue module of 555 genes was affected by exposure (p = 0.0023) and strongly correlated with FEV _0.05 /FVC (r = 0.61 and p = 3E-5).
Conclusions: This study aims to fill in a major knowledge gap and investigated the effect of PM _2.5 exposure simultaneously in multiple tissues. We provided novel evidence that PM _2.5 NO ₃ ^- exposure profoundly perturbed within- and cross-tissue gene regulations, and highlighted their roles in the etiology of respiratory decline.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)