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. 2022 Sep 8;11(18):2810. doi: 10.3390/cells11182810

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© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Cigarette smoke plus morphine, morphine, and smoke modulate the expression of transcription factors (TFs). (A,B) The ingenuity pathway analysis (IPA) showed that SM + M, M, and SM specifically upregulated 70, 16, and 24 and downregulated 75, 39, and 12 IPA-annotated TFs in Tregs, respectively. (C–E) The metascape pathway analysis of the specifically upregulated genes in SM + M, M, and SM, respectively. (F) SM + M, M, and SM modulated the expressions of 22, 17, and 14 out of 149 inducible Treg (iTreg)-specific TFs and 14, 8, and 5 out of 78 iTregs-Th17-shared TFs in mouse splenic Tregs, respectively. (G) The heat map was generated by using the value of log2FC of the TFs (p-value < 0.05) in each comparison. The results showed that: (1) SM + M significantly upregulates the expression of four inducible Treg (iTregs)TFs including HDAC5, YAF2, MXD4, and PBXIP1, which were not upregulated in SM treated Tregs and M treated Tregs (red arrow). In addition, SM + M upregulated three iTreg and Th17 shared TFs (red arrows) including PYCARD, PTTG1, PDZ, and PDLIM1; (2) SM upregulated TF ATF5 (green arrow) is SM specific; and (3) seven M downregulated TFs including CSRNP1, CEBPB, CREM, MXD1, FOXP3, IKZF4, TSC22D3 are M specific. (H) The metascape pathway analysis for SM + M 15 upregulated iTreg-specific TFs. (I) The Venn diagram analysis indicated that SM + M Tregs overlaps one TF pathway with that of SM Tregs TFs and M Tregs TFs; SM + M Tregs TFs overlap three TF pathways with that of SM Tregs TFs, and SM Tregs TFs overlaps one TF pathway with that of iTregs TFs. (J) SM + M, M, and SM downregulated the expression of Rel (c-Rel) in Tregs (p < 0.05). (K) 35 genes out of 1354 SM + M downregulated genes were overlapped with Rel-deficient Tregs downregulated gene.

Cigarette smoke plus morphine, morphine, and smoke modulate the expression of transcription factors (TFs). (A,B) The ingenuity pathway analysis (IPA) showed that SM + M, M, and SM specifically upregulated 70, 16, and 24 and downregulated 75, 39, and 12 IPA-annotated TFs in Tregs, respectively. (C–E) The metascape pathway analysis of the specifically upregulated genes in SM + M, M, and SM, respectively. (F) SM + M, M, and SM modulated the expressions of 22, 17, and 14 out of 149 inducible Treg (iTreg)-specific TFs and 14, 8, and 5 out of 78 iTregs-Th17-shared TFs in mouse splenic Tregs, respectively. (G) The heat map was generated by using the value of log2FC of the TFs (p-value < 0.05) in each comparison. The results showed that: (1) SM + M significantly upregulates the expression of four inducible Treg (iTregs)TFs including HDAC5, YAF2, MXD4, and PBXIP1, which were not upregulated in SM treated Tregs and M treated Tregs (red arrow). In addition, SM + M upregulated three iTreg and Th17 shared TFs (red arrows) including PYCARD, PTTG1, PDZ, and PDLIM1; (2) SM upregulated TF ATF5 (green arrow) is SM specific; and (3) seven M downregulated TFs including CSRNP1, CEBPB, CREM, MXD1, FOXP3, IKZF4, TSC22D3 are M specific. (H) The metascape pathway analysis for SM + M 15 upregulated iTreg-specific TFs. (I) The Venn diagram analysis indicated that SM + M Tregs overlaps one TF pathway with that of SM Tregs TFs and M Tregs TFs; SM + M Tregs TFs overlap three TF pathways with that of SM Tregs TFs, and SM Tregs TFs overlaps one TF pathway with that of iTregs TFs. (J) SM + M, M, and SM downregulated the expression of Rel (c-Rel) in Tregs (p < 0.05). (K) 35 genes out of 1354 SM + M downregulated genes were overlapped with Rel-deficient Tregs downregulated gene.