4.7 Article

IL-33 priming and antigenic stimulation synergistically promote the transcription of proinflammatory cytokine and chemokine genes in human skin mast cells

Journal

BMC GENOMICS
Volume 24, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12864-023-09702-w

Keywords

Human skin mast cells; IgE receptor cross-linking; IL-33 priming; Chromatin accessibility; RNA-seq analysis; Pro-inflammatory cytokine and chemokine genes

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Our study shows that IL-33 priming significantly enhances the transcription of proinflammatory cytokine and chemokine genes in MCs in response to antigenic stimulation, shedding light on the exacerbation of skin MC-mediated allergic inflammation by epithelial cell-derived cytokine IL-33.
BackgroundAntigenic stimulation through cross-linking the IgE receptor and epithelial cell-derived cytokine IL-33 are potent stimuli of mast cell (MC) activation. Moreover, IL-33 primes a variety of cell types, including MCs to respond more vigorously to external stimuli. However, target genes induced by the combined IL-33 priming and antigenic stimulation have not been investigated in human skin mast cells (HSMCs) in a genome-wide manner. Furthermore, epigenetic changes induced by the combined IL-33 priming and antigenic stimulation have not been evaluated.ResultsWe found that IL-33 priming of HSMCs enhanced their capacity to promote transcriptional synergy of the IL1B and CXCL8 genes by 16- and 3-fold, respectively, in response to combined IL-33 and antigen stimulation compared to without IL-33 priming. We identified the target genes in IL-33-primed HSMCs in response to the combined IL-33 and antigenic stimulation using RNA sequencing (RNA-seq). We found that the majority of genes synergistically upregulated in the IL-33-primed HSMCs in response to the combined IL-33 and antigenic stimulation were predominantly proinflammatory cytokine and chemokine genes. Moreover, the combined IL-33 priming and antigenic stimulation increase chromatin accessibility in the synergy target genes but not synergistically. Transcription factor binding motif analysis revealed more binding sites for NF-kappa B, AP-1, GABPA, and RAP1 in the induced or increased chromatin accessible regions of the synergy target genes.ConclusionsOur study demonstrates that IL-33 priming greatly potentiates MCs' ability to transcribe proinflammatory cytokine and chemokine genes in response to antigenic stimulation, shining light on how epithelial cell-derived cytokine IL-33 can cause exacerbation of skin MC-mediated allergic inflammation.

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