Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA350337 | ENA |
REPOSITORIES: ENA
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Project description:TL1A contributes to the pathogenesis of several chronic inflammatory diseases, including Inflammatory Bowel Diseases by enhancing TH1, TH17, and TH2 responses. TL1A mediates a strong co-stimulation of these TH subsets particularly of mucosal CCR9+ T cells. However, the signaling pathways that TL1A induces in different TH subsets are incompletely understood. Here, we investigated the function of TL1A on human TH17 cells. TL1A together with TGF- IL-6, and IL-23 enhanced the secretion of IL-17 and IFN- from human CD4+ memory T cells. TL1A induced the expression of the transcription factors BATF and T-bet that correlated with the secretion of IL-17 and IFN-. In contrast, TL1A alone induced high levels of IL-22 in memory CD4+ T cells and committed TH17 cells. However, TL1A did not enhance expression of IL-17A in TH17 cells. Expression of the transcription factor aryl hydrocarbon receptor that regulates expression of IL-22 was not affected by TL1A. We performed transcriptome analysis of TH17 cells to determine genes that are transcriptionally regulated by TL1A. transcriptome analysis revealed increased expression of IL-9 in response to TL1A.
2016-10-25 | GSE89133 | GEO
Project description:T helper 9 (TH9) cells are important for the development of inflammatory and allergic diseases. The TH9 transcriptional network converge signals from cytokines and antigen presentation but is incompletely understood. Here, we identified TL1A, a member of the TNF superfamily, as strong inducer of mouse and human TH9 differentiation. Mechanistically, TL1A induced the expression of the transcription factors BATF and BATF3 and facilitated their binding to the Il9 promoter leading to enhanced secretion of IL-9. BATF- and BATF3-deficiencies impaired IL-9 secretion under TH9 and TH9-TL1A polarizing conditions. In vivo, using a T cell transfer model we demonstrated that TL1A promoted IL-9-dependent, TH9 cell-induced intestinal and lung inflammation. Neutralizing IL-9 antibodies attenuated TL1A-driven mucosal inflammation. Batf3-/- TH9-TL1A cells induced reduced inflammation and cytokine expression in vivo compared to WT cells. Our results demonstrate that TL1A promotes TH9 cell differentiation and function and define a role of BATF3 in TH9-induced mucosal inflammation.
2019-01-08 | GSE106926 | GEO
Project description:The TNF family member TL1A (TNFSF15) co-stimulates several T helper subsets and promotes T cell-dependent models of inflammatory diseases, including inflammatory bowel diseases (IBD) and allergic lung disease. TL1A polymorphisms confer susceptibility to IBD and have been associated with disease severity. In this study, we identified TL1A as a strong inducer of TH9 cell differentiation in vitro. Mechanistically, TL1A induced NF-B signaling and down-stream STAT6 activation and facilitated cooperative binding of BATF, BATF3, and IRF4 to the Il9 promoter. In vivo, utilizing an adoptive T cell transfer model we demonstrated that TL1A promoted IL-9-dependent, TH9 cell-induced intestinal and lung inflammation and blocking anti-IL-9 antibodies attenuated TL1A-driven mucosal inflammation. Our results demonstrate that TL1A promotes TH9 cell differentiation and function and define a role for IL-9 in TL1A-induced mucosal inflammation.
2019-01-08 | GSE60362 | GEO
Project description:We analyzed the total proteome of group 2 innate lymphoid cells (ILC2s) after different stimulation with interleukin-33 (IL-33), a cytokine playing a critical role in human asthma, and TL1A, a TNF-family cytokine also known to activate ILC2s. Upon combined stimulation with IL-33 plus TL1A, we show that lung ILC2s produce high amounts of IL-9 and acquire a transient ‘ILC9’ phenotype. This phenotype is characterized by simultaneous production of large amounts of type 2 cytokines (IL-5, IL-13 and IL-9), induction of the IL-2 receptor CD25 (Il2ra), and of the transcription factors IRF4, JunB and BATF, that form immune-specific complexes known to induce IL-9 expression.
2024-03-05 | PXD041987 | Pride
Project description:TNF-like ligand 1A (TL1A) is a member of TNF receptor superfamily and involved in the pathogenesis of autoimmune diseases by inducing apoptosis via intracellular death domain or promoting inflammation through the activation of NFM-NM-:B by binding to its specific receptor death receptor 3 (DR3). Meanwhile, decoy receptor 3 (DcR3) competitively binds soluble TL1A in addition to Fas-ligand (FasL) and LIGHT and inhibits the signaling of TL1A via DR3. DcR3 overexpressed in rheumatoid synovial fibroblasts (RA-FLS) stimulated with inflammatory cytokines such as TNFM-NM-1 or IL-1M-NM-2 inhibits Fas-induced apoptosis. In contrast, DcR3 inhibited cell proliferation induced by inflammatory cytokines via membrane-bound TL1A expressed on RA-FLS. Therefore, TL1A-DcR3/DR3 signaling may be involved in the pathogenesis of RA by modulating apoptosis and proliferation of RA-FLS. We hypothesized that TL1A regulates the gene expression in RA-FLS. We used to search for genes in which expression in RA-FLS is regulated by the ligation of TL1A. RA-FLS were obtained from 4 RA patients (sample1-4). Each sample was incubated with either 1.0 M-NM-<g/ml recombinant human TL1A protein or phosphate buffered saline (PBS) diluted with serum-free Opti-MEM medium as non-stimulated control for 12 hours at 37M-BM-0C with 5% CO2. Gene expression in RA-FLS stimulated by TL1A was compared with that of their respective non-stimulated controls.
2014-12-10 | E-GEOD-63995 | biostudies-arrayexpress
Project description:TNF-like ligand 1A (TL1A) is a member of TNF receptor superfamily and involved in the pathogenesis of autoimmune diseases by inducing apoptosis via intracellular death domain or promoting inflammation through the activation of NFκB by binding to its specific receptor death receptor 3 (DR3). Meanwhile, decoy receptor 3 (DcR3) competitively binds soluble TL1A in addition to Fas-ligand (FasL) and LIGHT and inhibits the signaling of TL1A via DR3. DcR3 overexpressed in rheumatoid synovial fibroblasts (RA-FLS) stimulated with inflammatory cytokines such as TNFα or IL-1β inhibits Fas-induced apoptosis. In contrast, DcR3 inhibited cell proliferation induced by inflammatory cytokines via membrane-bound TL1A expressed on RA-FLS. Therefore, TL1A-DcR3/DR3 signaling may be involved in the pathogenesis of RA by modulating apoptosis and proliferation of RA-FLS. We hypothesized that TL1A regulates the gene expression in RA-FLS. We used to search for genes in which expression in RA-FLS is regulated by the ligation of TL1A.
2014-12-10 | GSE63995 | GEO
Project description:Th subsets are defined according to their production of lineage-indicating cytokines and functions. In this study, we have identified a subset of human Th cells that infiltrates the epidermis in individuals with inflammatory skin disorders and is characterized by the secretion of IL-22 and TNF-a, but not IFN-g, IL-4, or IL-17. In analogy to the Th17 subset, cells with this cytokine profile have been named the Th22 subset. Th22 clones derived from patients with psoriasis were stable in culture and exhibited a transcriptome profile clearly separate from those of Th1, Th2, and Th17 cells; it included genes encoding proteins involved in tissue remodeling, such as FGFs, and chemokines involved in angiogenesis and fibrosis. Primary human keratinocytes exposed to Th22 supernatants expressed a transcriptome response profile that included genes involved in innate immune pathways and the induction and modulation of adaptive immunity. These proinflammatory Th22 responses were synergistically dependent on IL-22 and TNF-a. Furthermore, Th22 supernatants enhanced wound healing in an in vitro injury model, which was exclusively dependent on IL-22. In conclusion, the human Th22 subset may represent a separate T cell subset with a distinct identity with respect to gene expression and function, present within the epidermal layer in inflammatory skin diseases. Future strategies directed against the Th22 subset may be of value in chronic inflammatory skin disorders.
2017-08-16 | GSE102641 | GEO
Project description:TNF-like ligand 1A (TL1A) is a member of TNF receptor superfamily and involved in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) by inducing apoptosis via intracellular death domain or promoting inflammation through the activation of NFκB by binding to its specific receptor death receptor 3 (DR3). Meanwhile, decoy receptor 3 (DcR3) competitively binds soluble TL1A in addition to Fas-ligand (FasL) and LIGHT and inhibits the signaling of TL1A via DR3. Therefore, TL1A-DcR3/DR3 signaling may be involved in the pathogenesis of RA by modulating apoptosis and proliferation of RA-FLS. We hypothesized that TL1A regulates the gene expression in RA-FLS. We used to search for genes in which expression in RA-FLS is regulated by TL1A.
2018-08-24 | GSE118958 | GEO
Project description:Inflammatory bowel disease (IBD) results from a dysregulated interaction between the microbiota and a genetically susceptible host. Genetic studies have linked TNFSF15 polymorphisms and its protein TNF-like ligand 1A (TL1A) with IBD, but the functional role of TL1A in linking tissue homeostasis and intestinal inflammation is not known. Here, using cell-specific genetic deletion models, we report an essential role for CX3CR1+ mononuclear phagocyte (MNP)-derived TL1A, which is induced by adherent IBD-associated microbiota, in regulating group 3 innate lymphoid cell (ILC3) production of IL-22 and mucosal healing in acute colitis. However, in contrast to this protective role in acute colitis, TL1A-dependent expression of OX40L in MHCII+ ILC3 during colitis leads to co-stimulation of antigen-specific T cells and is required for chronic T cell colitis. These results identify a new role for ILC3 in regulating intestinal T cells and reveal a central role for TL1A in regulating ILC3 barrier immunity during colitis.
2018-12-26 | GSE120723 | GEO
Project description:Asthma, a heterogeneous disease, is characterized by chronic inflammation, epithelial–mesenchymal transformation (EMT), and airway remodeling. After immune system activation, macrophages, T cells, and other cells gather and secrete various factors, such as interleukin-1β, 4, 5, 10, 13, and TNF-a, which break the anti-inflammatory balance and aggravate the progression of asthma. TNF-a, a member of the TNF superfamily, has promising future in the pathophysiological progress of autoimmune diseases and the development and application of related drugs. However, the mechanisms of TNF-a in mucus secretion, airway hyperreactivity, and airway remodeling of human asthma remains unclear. Tumor necrosis factor-like cytokine 1A is a type II transmembrane protein with a stable trimer structure similar to TNF-a. Migone et al. first uncovered the presence of TL1A as a membrane-bound protein (mTL1A) or a soluble protein (sTL1A) from mTL1A cleaved by an underlying enzyme. DR3 is a type I membrane protein that contains a death domain in the cytoplasmic region and remains highly homologous with other TNFRSF members. Interestingly, Evangelos et al. found that TNF-a-stimulated human lung myofibroblasts significantly increase TL1A expression and collagen production. Our study will identify the specific role of TNF-a-stimulated mTL1A/DR3 or sTL1A/DR3 axis in the EMT of asthma model.
2022-05-20 | PXD031079 | Pride