Data from: Dietary docosahexaenoic acid supplementation inhibits acute pulmonary transcriptional and autoantibody responses to a single crystalline silica exposure in lupus-prone mice

<p>Short-term repeated intranasal exposure crystalline silica (cSiO₂), a known human autoimmune trigger, induces uncontrolled inflammation, upregulated IFN-stimulated gene expression, diverse autoantibody production, and glomerulonephritis in lupus-prone female NZBWF1 mice. Dietary supplementation with the omega-3 fatty acid docosahexaenoic acid (DHA) prevents subchronic cSiO₂ triggering of these lupus hallmarks. To understand how this intervention impacts acute effects of cSiO₂, we fed NZBWF1 mice control (CON) or DHA-containing diet, subjected them to a single acute intranasal instillation of 2.5 mg cSiO₂, then compared pulmonary inflammatory/autoimmune responses and autoimmune-related gene expression in experimental cohorts terminated at 7 and 28 d post-instillation (PI). Acute cSiO₂exposure of CON-fed mice elicited decreased macrophage and increased neutrophil numbers at 7 d PI, whereas at 28 d PI, CON-fed mice treated with particle displayed elevated total cell, macrophage, neutrophil, and lymphocyte counts. In contrast, DHA-fed mice treated with cSiO₂ exhibited less macrophage loss at 7 d PI and reduced total cell, macrophage, and lymphocyte accumulation at 28 d PI. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) of lung sections suggested that cSiO₂ induced more robust cell death at 7 d PI in CON-fed than DHA-fed mice. Targeted multiplex ELISA of lung extracts showed that at 28 d PI, cSiO₂ induced higher concentrations of inflammation-associated cytokines (IL-1α, IL-6, and GM-CSF) and IFN-stimulated chemokines (CCL2, CCL3, CXCL10) in the CON-fed cohort than in the DHA-fed cohort. Autoantigen protein microarray of BALF collected at 28 d PI indicated that cSiO₂ induced higher autoantibody responses for representative nuclear, ribosomal, mitochondrial, and complement proteins in CON-fed mice than DHA-fed mice. Gene expression analyses with NanoString Autoimmune Gene Expression assay revealed greater cSiO₂-triggered upregulation of genes associated with TLR activation, DNA signaling, proinflammatory cytokines,  chemokines, type 1 and 2 IFN response signatures, lymphocyte trafficking, MHC class 1 antigen presentation, B and T cell activation at 7 and 28 d PI in CON-fed mice than those fed DHA. Ingenuity Pathway Analysis (IPA) further demonstrated that DHA supplementation quelled cSiO₂-induced responses top upstream regulators of proinflammatory and IFN-regulated gene networks to observed in CON-fed mice. Altogether, this short-term model illustrated that DHA suppression of aberrant acute cSiO₂-induced inflammation is linked to altered regulation of autoimmune-related gene expression in lupus-prone mice.</p>