IL-1β induces the rapid secretion of the antimicrobial protein IL-26 from Th17 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE127457 | GEO | 2019/06/07
REPOSITORIES: GEO
Similar Datasets
Project description:IL-1β induces the rapid secretion of the antimicrobial protein IL-26 from Th17 cells
| PRJNA524825 | ENA
Project description:Th17 cells play a critical role in the adaptive immune response against extracellular bacteria, and the possible mechanisms by which they can protect against infection are of particular interest. In this study, we describe, to our knowledge, a novel IL-1β dependent pathway for secretion of the antimicrobial peptide IL-26 from human Th17 cells that is independent of and more rapid than classical TCR activation. We find that IL-26 is secreted 3 hours after treating PBMCs with Mycobacterium leprae as compared with 48 hours for IFN-γ and IL-17A. IL-1β was required for microbial ligand induction of IL-26 and was sufficient to stimulate IL-26 release from Th17 cells. Only IL-1RI+ Th17 cells responded to IL-1β, inducing an NF-κB-regulated transcriptome. Finally, supernatants from IL-1β-treated memory T cells killed Escherichia coli in an IL-26-dependent manner. These results identify a mechanism by which human IL-1RI+ "antimicrobial Th17 cells" can be rapidly activated by IL-1β as part of the innate immune response to produce IL-26 to kill extracellular bacteria.
| S-EPMC6684376 | biostudies-literature
Project description:Toll-like receptors/Interleukin-1 receptor (IL-1R) signaling plays an important role in High-fat diet (HFD)-induced adipose tissue dysfunction contributing to obesity-associated metabolic syndromes. Here, we show an unconventional IL-1R-IRAKM (IL-1R-associated kinase M)-Slc25a1 signaling axis in adipocytes that reprograms lipogenesis to promote diet-induced obesity. Adipocyte-specific deficiency of IRAKM reduced HFD-induced body weight gain, increased whole body energy expenditure and improved insulin resistance, associated with decreased lipid accumulation and adipocyte cell sizes. IL-1β stimulation induced the translocation of IRAKM Myddosome to mitochondria to promote de novo lipogenesis in adipocytes. Mechanistically, IRAKM interacts with and phosphorylates mitochondrial citrate carrier Slc25a1 to promote IL-1β-induced mitochondrial citrate transport to cytosol and de novo lipogenesis. Moreover, IRAKM-Slc25a1 axis mediates IL-1β induced Pgc1a acetylation to regulate thermogenic gene expression in adipocytes. IRAKM kinase-inactivation also attenuated HFD-induced obesity. Taken together, our study suggests that the IL-1R-IRAKM-Slc25a1 signaling axis tightly links inflammation and adipocyte metabolism, indicating a novel therapeutic target for obesity.
2022-06-09 | PXD031934 | Pride
Project description:Antagonizing IL-1β to treat GBM
| PRJNA824138 | ENA
Project description:Atopic dermatitis (AD) is a debilitating inflammatory skin disorder. Biologics targeting the IL-4/IL-13 axis are effective in AD, but there is still a large proportion of patients that do not respond to IL-4R blockade. Further exploration of potentially pathogenic T cell-derived cytokines in AD may lead to new effective treatments. This study aimed to investigate the downstream effects of IL-26 on skin in the context of type 2 skin inflammation. We found that IL-26 alone exhibited limited inflammatory activity in skin. However, in presence of IL-1β, IL-26 potentiated the secretion of TSLP, CXCL1 and CCL20 from human epidermis through JAK/STAT signaling. Moreover, in an in vivo AD-like skin inflammation model, IL-26 exacerbated skin pathology and locally increased type 2 cytokines, most notably of Il13 in skin T helper cells. Neutralization of IL-1β abrogated IL-26-mediated effects, indicating that the presence of IL-1β is required for full IL-26 downstream action in vivo. These findings suggest that the presence of IL-1β enables IL-26 to be a key amplifier of inflammation in the skin. As such, IL-26 may contribute to the development and pathogenesis of inflammatory skin disorders such as AD.
2024-01-10 | GSE228860 | GEO
Project description:Interleukin-1 (IL-1) is a key pro-inflammatory cytokine, which has diverse actions in the brain as a regulator of host defence responses and a mediator of inflammation. Two major agonists, IL-1α and IL-1β bind to a single known functional (type-1) IL-1 receptor (IL-1RI), which associates with an accessory protein (IL-1RAcP) leading to signal transduction. However, recent evidence suggests that some actions of IL-1 in the brain may be independent of IL-1R1 and its classical signalling pathways, pointing to an as yet unidentified functional receptor for IL-1 expressed in the CNS. In this study, cDNA array based gene expression profiling was used to identify possible genes induced by IL-1β independently of IL-1R1. The results show that IL-1β may indeed regulate some genes independently of IL-1R1, suggesting the presence of additional functional IL-1 receptors in the mouse brain. Keywords: experimental treatment (IL-1β), gene ablation (IL-1R1), glia
2006-03-25 | GSE4507 | GEO
Project description:The canonical pathway for IL-1β production requires TLR-mediated NF-κB-dependent Il1b gene induction, followed by caspase-containing inflammasome-mediated processing of pro-IL-1β. Here we show that IL-21 unexpectedly induces IL-1β production in conventional dendritic cells (cDCs) via a STAT3-dependent but NF-κB-independent pathway. IL-21 does not induce Il1b expression in CD4+ T cells, with differential histone marks present in these cells versus cDCs. IL-21-induced IL-1β processing in cDCs does not require caspase-1 or caspase-8 but depends on IL-21-mediated death and activation of serine protease(s). Moreover, STAT3-dependent IL-1β expression in cDCs at least partially explains the IL-21-mediated pathologic response occurring during infection with Pneumonia Virus of Mice. These results demonstrate lineage-restricted IL-21-induced IL-1β via a non-canonical pathway and provide evidence for its importance in vivo.
2015-07-07 | GSE61677 | GEO
Project description:To gain a better understanding of the role of Interleukin-1β (IL-1β) in lung CD140a+ mesenchymal cells (fibroblasts) modulation, we performed RNA-seq to compare the transcriptomes of IL-1β-treated and control lung CD140a+ mesenchymal cells (fibroblasts).
2022-07-19 | E-MTAB-11887 | biostudies-arrayexpress
Project description:In the context of T1 Diabetes, pro-inflammatory cytokines IL-1β and IFN-γ are known to contribute to β-cell apoptosis; The measurement of mRNA expression following β-cell exposure to these cytokines gives a picture of the changes in gene expression characterizing the path to β-cell dysfunction and death. Human islets were isolated and exposed (or not) to IL-1β and IFN-γ. The samples were collected at various time points for profiling with Affymetrix arrays. These measurements were performed three times.
2013-12-19 | E-GEOD-53454 | biostudies-arrayexpress
Project description:Caspase-1 signaling in myeloid suppressor cells can promote T-cell independent cancer progression, but the regulation of inflammasome signaling within the highly heterogeneous myeloid cells in the tumor milieu remains elusive. To resolve this complexity, scRNA-seq of human head & neck carcinoma identified distinct inflammasome complex genes within specific clusters of tumor-infiltrating myeloid cells. Among these myeloid cells, NLRP3 sensor and downstream effector IL-1β transcripts were enriched in multiple monocytic and macrophage subtypes in the TME. In vivo, we showed that NLRP3, and not AIM2, phenocopied the caspase-1/IL-1β dependent tumor progression. Paradoxically, we found that myeloid-intrinsic caspase-1 signaling within the TME increased myeloid survival without significant intratumoral trafficking as would be predicted from their canonical pyroptotic function. Mechanistically, this myeloid NLRP3/IL-1β signaling axis promotion of tumor growth was found to be gasdermin D independent. When we probed for the tumor intrinsic factors that regulated NLRP3/IL-1β signaling, we found that mononuclear phagocyte-mediated efferocytosis of dying tumor cells in the TME directly activated NLRP3 dependent inflammasome signaling to drive IL-1β secretion and to promote tumor growth. Dynamic RNA velocity analysis of the single cell transcriptomic dataset showed a strong directional flow from efferocytosis gene-sethigh macrophages to an inflammasome gene-sethigh macrophage population. Cumulatively, we provide a novel inflammasome signaling axis between tumor apoptosis and myeloid cells that characterizes chronic inflammation induced malignancy.
2022-04-13 | GSE200560 | GEO