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Identifying Hub Genes, Key Pathways and Immune Cell Infiltration Characteristics in Pediatric and Adult Ulcerative Colitis by Integrated Bioinformatic Analysis

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Abstract

Background and Aims

In the present study, we investigated the differentially expressed genes (DEGs), pathways and immune cell infiltration characteristics of pediatric and adult ulcerative colitis (UC).

Methods

We conducted DEG analysis using the microarray dataset GSE87473 containing 19 pediatric and 87 adult UC samples downloaded from the Gene Expression Omnibus. Gene ontology and pathway enrichment analyses were conducted using Metascape. We constructed the protein–protein interaction (PPI) network and the drug–target interaction network of DEGs and identified hub modules and genes using Cytoscape and analyzed immune cell infiltration in pediatric and adult UC using CIBERSORT.

Results

In total, 1700 DEGs were screened from the dataset. These genes were enriched mainly in inter-cellular items relating to cell junctions, cell adhesion, actin cytoskeleton and transmembrane receptor signaling pathways and intra-cellular items relating to the splicing, metabolism and localization of RNA. CDC42, POLR2A, RAC1, PIK3R1, MAPK1 and SRC were identified as hub DEGs. Immune cell infiltration analysis revealed higher proportions of naive B cells, resting memory T helper cells, regulatory T cells, monocytes, M0 macrophages and activated mast cells in pediatric UC, along with lower proportions of memory B cells, follicular helper T cells, γδ T cells, M2 macrophages, and activated dendritic cells.

Conclusions

Our study suggested that hub genes CDC42, POLR2A, RAC1, PIK3R1, MAPK1 and SRC and immune cells including B cells, T cells, monocytes, macrophages and mast cells play vital roles in the pathological differences between pediatric and adult UC and may serve as potential biomarkers in the diagnosis and treatment of UC.

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Availability of data and materials

The dataset generated and/or analyzed during the current study are available from the Gene Expression Omnibus repository GSE87473.

References

  1. Sauer CG, Kugathasan S. Pediatric inflammatory bowel disease: highlighting pediatric differences in IBD. Med Clin North Am. 2010;94:35-52.

    Article  CAS  PubMed  Google Scholar 

  2. Van Limbergen J, Russell RK, Drummond HE, Aldhous MC, Round NK, Nimmo ER et al. Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. Gastroenterology. 2008;135:1114-1122.

    Article  PubMed  Google Scholar 

  3. Turner D, Walsh CM, Benchimol EI, Mann EH, Thomas KE, Chow C et al. Severe paediatric ulcerative colitis: incidence, outcomes and optimal timing for second-line therapy. Gut. 2008;57:331-338.

    Article  CAS  PubMed  Google Scholar 

  4. Duricova D, Leroyer A, Savoye G, Sarter H, Pariente B, Aoucheta D et al. Extra-intestinal manifestations at diagnosis in paediatric- and elderly-onset ulcerative colitis are associated with a more severe disease outcome: a population-based study. J Crohns Colitis. 2017;11:1326-1334.

    Article  PubMed  Google Scholar 

  5. Malaty HM, Mehta S, Abraham B, Garnett EA, Ferry GD. The natural course of inflammatory bowel disease-indeterminate from childhood to adulthood: within a 25 year period. Clin Exp Gastroenterol. 2013;6:115-121.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Aloi M, D'Arcangelo G, Pofi F, Vassallo F, Rizzo V, Nuti F et al. Presenting features and disease course of pediatric ulcerative colitis. J Crohns Colitis. 2013;7:e509-515.

    Article  PubMed  Google Scholar 

  7. Dan T, Levine A, Escher JC, Griffiths AM, Ruemmele FM. Management of pediatric ulcerative colitis: joint ECCO and ESPGHAN evidence-based consensus guidelines. J Pediatr Gastroenterol Nutr. 2012;55:340-361.

    Article  CAS  Google Scholar 

  8. Ruemmele FM, Turner D. Differences in the management of pediatric and adult onset ulcerative colitis--lessons from the joint ECCO and ESPGHAN consensus guidelines for the management of pediatric ulcerative colitis. J Crohns Colitis. 2014;8:1-4.

    Article  PubMed  Google Scholar 

  9. Ouahed J, Gordon W, Canavan JB, Zhou H, Du S, von Schack D et al. Mucosal gene expression in pediatric and adult patients with ulcerative colitis permits modeling of ideal biopsy collection strategy for transcriptomic analysis. Inflamm Bowel Dis. 2018;24:2565-2578.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Li K, Strauss R, Ouahed J, Chan D, Telesco SE, Shouval DS et al. Molecular comparison of adult and pediatric ulcerative colitis indicates broad similarity of molecular pathways in disease tissue. J Pediatr Gastroenterol Nutr. 2018;67:45-52.

    Article  CAS  PubMed  Google Scholar 

  11. Savic Mlakar A, Hojsak I, Jergovic M, Vojvoda Parcina V, Babic Z, Troskot B et al. Comparison of cytokine and efflux transporter expression in pediatric versus adult-onset ulcerative colitis. J Pediatr Gastroenterol Nutr. 2017;64:943-948.

    Article  PubMed  CAS  Google Scholar 

  12. Tatiya-Aphiradee N, Chatuphonprasert W, Jarukamjorn K. Immune response and inflammatory pathway of ulcerative colitis. J Basic Clin Physiol Pharmacol. 2018;30:1-10.

    Article  PubMed  CAS  Google Scholar 

  13. Neurath MF. Targeting immune cell circuits and trafficking in inflammatory bowel disease. Nat Immunol. 2019;20:970-979.

    Article  CAS  PubMed  Google Scholar 

  14. Geremia A, Biancheri P, Allan P, Corazza GR, Di Sabatino A. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev. 2014;13:3-10.

    Article  CAS  PubMed  Google Scholar 

  15. Liu Z, Meng J, Li X, Zhu F, Liu T, Wu G et al. Identification of hub genes and key pathways associated with two subtypes of diffuse large B-cell lymphoma based on gene expression profiling via integrated bioinformatics. Biomed Res Int. 2018;2018:3574534.

    PubMed  PubMed Central  Google Scholar 

  16. Li X, Liu Z, Mi M, Zhang C, Xiao Y, Liu X et al. Identification of hub genes and key pathways associated with angioimmunoblastic T-cell lymphoma using weighted gene co-expression network analysis. Cancer Manag Res. 2019;11:5209-5220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Darbeheshti F, Rezaei N, Amoli MM, Mansoori Y, Tavakkoly Bazzaz J. Integrative analyses of triple negative dysregulated transcripts compared with non-triple negative tumors and their functional and molecular interactions. J Cell Physiol. 2019;234:22386-22399.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang J, Zhou YJ, Yu ZH, Chen AX, Yu Y, Wang X et al. Identification of core genes and clinical roles in pregnancy-associated breast cancer based on integrated analysis of different microarray profile datasets. Biosci Rep. 2019;39.

    Google Scholar 

  19. Kalamohan K, Periasamy J, Bhaskar Rao D, Barnabas GD, Ponnaiyan S, Ganesan K. Transcriptional coexpression network reveals the involvement of varying stem cell features with different dysregulations in different gastric cancer subtypes. Mol Oncol. 2014;8:1306-1325.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Qin G, Mallik S, Mitra R, Li A, Jia P, Eischen CM et al. MicroRNA and transcription factor co-regulatory networks and subtype classification of seminoma and non-seminoma in testicular germ cell tumors. Sci Rep. 2020;10:852.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12:453-457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M et al. NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res. 2013;41:D991-995.

    Article  CAS  PubMed  Google Scholar 

  23. Zhou Y, Zhou B, Pache L, Chang M, Khodabakhshi AH, Tanaseichuk O et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun. 2019;10:1523.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J et al. STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47:D607-d613.

    Article  CAS  PubMed  Google Scholar 

  25. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13:2498-2504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bader GD, Hogue CW. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinform. 2003;4:2.

    Article  Google Scholar 

  27. Assenov Y, Ramirez F, Schelhorn SE, Lengauer T, Albrecht M. Computing topological parameters of biological networks. Bioinformatics (Oxford, England). 2008;24:282-284.

    Article  CAS  Google Scholar 

  28. Cotto KC, Wagner AH, Feng YY, Kiwala S, Coffman AC, Spies G et al. DGIdb 3.0: a redesign and expansion of the drug-gene interaction database. Nucleic Acids Res. 2018;46:D1068-d1073.

    Article  CAS  PubMed  Google Scholar 

  29. Gao W, Wang C, Yu L, Sheng T, Wu Z, Wang X et al. Chlorogenic acid attenuates dextran sodium sulfate-induced ulcerative colitis in mice through MAPK/ERK/JNK pathway. Biomed Res Int. 2019;2019:6769789.

    PubMed  PubMed Central  Google Scholar 

  30. Lv Q, Qiao SM, Xia Y, Shi C, Xia YF, Chou GX et al. Norisoboldine ameliorates DSS-induced ulcerative colitis in mice through induction of regulatory T cells in colons. Int Immunopharmacol. 2015;29:787-797.

    Article  CAS  PubMed  Google Scholar 

  31. Cai L, Li X, Geng C, Lei X, Wang C. Molecular mechanisms of somatostatin-mediated intestinal epithelial barrier function restoration by upregulating claudin-4 in mice with DSS-induced colitis. Am J Physiol Cell Physiol. 2018;315:C527-C536.

    Article  CAS  PubMed  Google Scholar 

  32. Kim H, Banerjee N, Ivanov I, Pfent CM, Prudhomme KR, Bisson WH et al. Comparison of anti-inflammatory mechanisms of mango (Punica Granatum L.) and pomegranate (Punica Granatum L.) in a preclinical model of colitis. Mol Nutr Food Res. 2016;60:1912-1923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Li X, Cai L, Xu H, Geng C, Lu J, Tao L et al. Somatostatin regulates NHE8 protein expression via the ERK1/2 MAPK pathway in DSS-induced colitis mice. Am J Physiol Gastrointest Liver Physiol. 2016;311:G954-G963.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Shi L, Lin Q, Yang T, Nie Y, Li X, Liu B et al. Oral administration of Lentinus edodes beta-glucans ameliorates DSS-induced ulcerative colitis in mice via MAPK-Elk-1 and MAPK-PPARgamma pathways. Food Funct. 2016;7:4614-4627.

    Article  CAS  PubMed  Google Scholar 

  35. You BH, Chae HS, Song J, Ko HW, Chin YW, Choi YH. alpha-Mangostin ameliorates dextran sulfate sodium-induced colitis through inhibition of NF-kappaB and MAPK pathways. Int Immunopharmacol. 2017;49:212-221.

    Article  CAS  PubMed  Google Scholar 

  36. Babbin BA, Jesaitis AJ, Ivanov AI, Kelly D, Laukoetter M, Nava P et al. Formyl peptide receptor-1 activation enhances intestinal epithelial cell restitution through phosphatidylinositol 3-kinase-dependent activation of Rac1 and Cdc42. J Immunol. 2007;179:8112-8121.

    Article  CAS  PubMed  Google Scholar 

  37. Schlegel N, Meir M, Spindler V, Germer CT, Waschke J. Differential role of Rho GTPases in intestinal epithelial barrier regulation in vitro. J Cell Physiol. 2011;226:1196-1203.

    Article  CAS  PubMed  Google Scholar 

  38. Fu Y, Galan JE. A salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion. Nature. 1999;401:293-297.

    Article  CAS  PubMed  Google Scholar 

  39. Tang WJ, Peng KY, Tang ZF, Wang YH, Xue AJ, Huang Y. MicroRNA-15a—cell division cycle 42 signaling pathway in pathogenesis of pediatric inflammatory bowel disease. World J Gastroenterol. 2018;24:5234-5245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Birkl D, Quiros M, Garcia-Hernandez V, Zhou DW, Brazil JC, Hilgarth R et al. TNFalpha promotes mucosal wound repair through enhanced platelet activating factor receptor signaling in the epithelium. Mucosal Immunol. 2019;12:909-918.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kato T, Suzuki K, Okada S, Kamiyama H, Maeda T, Saito M et al. Aberrant methylation of PSD disturbs Rac1-mediated immune responses governing neutrophil chemotaxis and apoptosis in ulcerative colitis-associated carcinogenesis. Int J Oncol. 2012;40:942-950.

    CAS  PubMed  Google Scholar 

  42. Wertheimer E, Kazanietz MG. Rac1 takes center stage in pancreatic cancer and ulcerative colitis: quantity matters. Gastroenterology. 2011;141:427-430.

    Article  PubMed  Google Scholar 

  43. Muise AM, Walters T, Xu W, Shen-Tu G, Guo CH, Fattouh R et al. Single nucleotide polymorphisms that increase expression of the guanosine triphosphatase RAC1 are associated with ulcerative colitis. Gastroenterology. 2011;141:633-641.

    Article  CAS  PubMed  Google Scholar 

  44. Samak G, Chaudhry KK, Gangwar R, Narayanan D, Jaggar JH, Rao R. Calcium/Ask1/MKK7/JNK2/c-Src signalling cascade mediates disruption of intestinal epithelial tight junctions by dextran sulfate sodium. Biochem J. 2015;465:503-515.

    Article  CAS  PubMed  Google Scholar 

  45. Seok Yang W, Lee J, Woong Kim T, Hye Kim J, Lee S, Hee Rhee M et al. Src/NF-kappaB-targeted inhibition of LPS-induced macrophage activation and dextran sodium sulphate-induced colitis by Archidendron clypearia methanol extract. J Ethnopharmacol. 2012;142:287-293.

    Article  PubMed  Google Scholar 

  46. Saldi T, Cortazar MA, Sheridan RM, Bentley DL. Coupling of RNA polymerase ii transcription elongation with pre-mRNA splicing. J Mol Biol. 2016;428:2623-2635.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Fong N, Kim H, Zhou Y, Ji X, Qiu J, Saldi T et al. Pre-mRNA splicing is facilitated by an optimal RNA polymerase II elongation rate. Genes Dev. 2014;28:2663-2676.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Hasler R, Kerick M, Mah N, Hultschig C, Richter G, Bretz F et al. Alterations of pre-mRNA splicing in human inflammatory bowel disease. Eur J Cell Biol. 2011;90:603-611.

    Article  PubMed  CAS  Google Scholar 

  49. Thoo L, Noti M, Krebs P. Keep calm: the intestinal barrier at the interface of peace and war. Cell Death Dis. 2019;10:849.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Moulahoum H, Boumaza BMA, Ferrat M, Bounaama A, Djerdjouri B. Arsenic trioxide ameliorates murine colon inflammation through inflammatory cell enzymatic modulation. Naunyn Schmiedeberg's Arch Pharmacol. 2019;392:259-270.

    Article  CAS  Google Scholar 

  51. Singer M, Trugnan G, Chelbi-Alix MK. Arsenic trioxide reduces 2,4,6-trinitrobenzene sulfonic acid-induced murine colitis via nuclear factor-kappaB down-regulation and caspase-3 activation. Innate immunity. 2011;17:365-374.

    Article  CAS  PubMed  Google Scholar 

  52. Ward JBJ, Lajczak NK, Kelly OB, O'Dwyer AM, Giddam AK, Ni Gabhann J et al. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon. Am J Physiol Gastrointest Liver Physiol. 2017;312:G550-g558.

    Article  PubMed  Google Scholar 

  53. Martinez-Moya P, Romero-Calvo I, Requena P, Hernandez-Chirlaque C, Aranda CJ, Gonzalez R et al. Dose-dependent antiinflammatory effect of ursodeoxycholic acid in experimental colitis. Int Immunopharmacol. 2013;15:372-380.

    Article  CAS  PubMed  Google Scholar 

  54. Kim HS. Prevention of colon cancer with ursodiol in ulcerative colitis. Inflamm Bowel Dis. 2001;7:279-280.

    Article  CAS  PubMed  Google Scholar 

  55. Croog VJ, Ullman TA, Itzkowitz SH. Chemoprevention of colorectal cancer in ulcerative colitis. Int J Colorectal Dis. 2003;18:392-400.

    Article  PubMed  Google Scholar 

  56. Can G, Ayvaz S, Can H, Karaboga I, Demirtas S, Aksit H et al. The efficacy of tyrosine kinase inhibitor dasatinib on colonic mucosal damage in murine model of colitis. Clin Res Hepatol Gastroenterol. 2016;40:504-516.

    Article  CAS  PubMed  Google Scholar 

  57. Tolstanova HM, Khomenko TA, Ostapchenko LI, Szabo S, Sandor Z. [The role of Src-tyrosine kinases in increasing vascular permeability during experimental ulcerative colitis]. Ukrains'kyi biokhimichnyi zhurnal (1999 ). 2010;82:117-122.

    Google Scholar 

  58. Biancheri P, Foster MR, Fyfe MC, MacDonald TT, Sirohi S, Solanke Y et al. Effect of narrow spectrum versus selective kinase inhibitors on the intestinal proinflammatory immune response in ulcerative colitis. Inflamm Bowel Dis. 2016;22:1306-1315.

    Article  PubMed  Google Scholar 

  59. Rabe H, Malmquist M, Barkman C, Ostman S, Gjertsson I, Saalman R et al. Distinct patterns of naive, activated and memory T and B cells in blood of patients with ulcerative colitis or Crohn's disease. Clin Exp Immunol. 2019;197:111-129.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Wang X, Jiang Y, Zhu Y, Zhang M, Li M, Wang H et al. Circulating memory B cells and plasmablasts are associated with the levels of serum immunoglobulin in patients with ulcerative colitis. J Cell Mol Med. 2016;20:804-814.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Wang X, Zhu Y, Zhang M, Hou J, Wang H, Jiang Y et al. The shifted balance between circulating follicular regulatory T cells and follicular helper T cells in patients with ulcerative colitis. Clin Sci (Lond). 2017;131:2933-2945.

    Article  CAS  Google Scholar 

  62. Xue G, Zhong Y, Hua L, Zhong M, Liu X, Chen X et al. Aberrant alteration of follicular T helper cells in ulcerative colitis patients and its correlations with interleukin-21 and B cell subsets. Medicine (Baltimore). 2019;98:e14757.

    Article  CAS  Google Scholar 

  63. Mohammadnia-Afrouzi M, Zavaran Hosseini A, Khalili A, Abediankenari S, Hosseini V, Maleki I. Decrease of CD4(+) CD25(+) CD127(low) FoxP3(+) regulatory T cells with impaired suppressive function in untreated ulcerative colitis patients. Autoimmunity. 2015;48:556-561.

    Article  CAS  PubMed  Google Scholar 

  64. Sang LX, Chang B, Zhu JF, Yang FL, Li Y, Jiang XF et al. Sodium selenite ameliorates dextran sulfate sodium-induced chronic colitis in mice by decreasing Th1, Th17, and gammadeltaT and increasing CD4(+)CD25(+) regulatory T-cell responses. World J Gastroenterol. 2017;23:3850-3863.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Wang S, Fan T, Yao L, Ma R, Yang S, Yuan F. Circulating follicular regulatory T cells could inhibit Ig production in a CTLA-4-dependent manner but are dysregulated in ulcerative colitis. Mol Immunol. 2019;114:323-329.

    Article  CAS  PubMed  Google Scholar 

  66. Tsuchiya T, Fukuda S, Hamada H, Nakamura A, Kohama Y, Ishikawa H et al. Role of gamma delta T cells in the inflammatory response of experimental colitis mice. J Immunol. 2003;171:5507-5513.

    Article  CAS  PubMed  Google Scholar 

  67. McVay LD, Li B, Biancaniello R, Creighton MA, Bachwich D, Lichtenstein G et al. Changes in human mucosal gamma delta T cell repertoire and function associated with the disease process in inflammatory bowel disease. Mol Med. 1997;3:183-203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Mann ER, Bernardo D, Ng SC, Rigby RJ, Al-Hassi HO, Landy J et al. Human gut dendritic cells drive aberrant gut-specific t-cell responses in ulcerative colitis, characterized by increased IL-4 production and loss of IL-22 and IFNγ. Inflamm Bowel Dis. 2014;20:2299-2307.

    Article  PubMed  Google Scholar 

  69. Al-Hassi HO, Mann ER, Sanchez B, English NR, Peake STC, Landy J et al. Altered human gut dendritic cell properties in ulcerative colitis are reversed by Lactobacillus plantarum extracellular encrypted peptide STp. Mol Nutr Food Res. 2014;58:1132-1143.

    Article  CAS  PubMed  Google Scholar 

  70. Gren ST, Grip O. Role of monocytes and intestinal macrophages in Crohn's disease and ulcerative colitis. Inflamm Bowel Dis. 2016;22:1992-1998.

    Article  PubMed  Google Scholar 

  71. Zhu Y, Li X, Chen J, Chen T, Shi Z, Lei M et al. The pentacyclic triterpene Lupeol switches M1 macrophages to M2 and ameliorates experimental inflammatory bowel disease. Int Immunopharmacol. 2016;30:74-84.

    Article  CAS  PubMed  Google Scholar 

  72. Lin Y, Yang X, Yue W, Xu X, Li B, Zou L et al. Chemerin aggravates DSS-induced colitis by suppressing M2 macrophage polarization. Cell Mol Immunol. 2014;11:355-366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Arranz A, Doxaki C, Vergadi E, Martinez de la Torre Y, Vaporidi K, Lagoudaki ED et al. Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization. Proc Natl Acad Sci USA. 2012;109:9517-9522.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Lissner D, Schumann M, Batra A, Kredel L-I, Kühl AA, Erben U et al. Monocyte and M1 macrophage-induced barrier defect contributes to chronic intestinal inflammation in IBD. Inflamm Bowel Dis. 2015;21:1297-1305.

    PubMed  Google Scholar 

  75. Zhu W, Yu J, Nie Y, Shi X, Liu Y, Li F et al. Disequilibrium of M1 and M2 macrophages correlates with the development of experimental inflammatory bowel diseases. Immunol Investig. 2014;43:638-652.

    Article  CAS  Google Scholar 

  76. Boeckxstaens G. Mast cells and inflammatory bowel disease. Curr Opin Pharmacol. 2015;25:45-49.

    Article  CAS  PubMed  Google Scholar 

  77. Casado-Bedmar M, Heil SDS, Myrelid P, Söderholm JD, Keita ÅV. Upregulation of intestinal mucosal mast cells expressing VPAC1 in close proximity to vasoactive intestinal polypeptide in inflammatory bowel disease and murine colitis. Neurogastroenterol Motil. 2019;31:e13503-e13503.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81760328).

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  1. Medical School of Nanchang University, 603 Bayi Road, Nanchang, 330006, Jiangxi, China

    Meng-xi Xiu, Yuan-meng Liu, Guang-yuan Chen, Cong Hu & Bo-hai Kuang

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MX and YL wrote the manuscript. GC, CH and BK coordinated and directed the project. All authors read and approved the manuscript.

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Correspondence to Bo-hai Kuang.

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Xiu, Mx., Liu, Ym., Chen, Gy. et al. Identifying Hub Genes, Key Pathways and Immune Cell Infiltration Characteristics in Pediatric and Adult Ulcerative Colitis by Integrated Bioinformatic Analysis. Dig Dis Sci 66, 3002–3014 (2021). https://doi.org/10.1007/s10620-020-06611-w

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