Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1087106 | ENA |
REPOSITORIES: ENA
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Project description:A body-brain circuit regulating body inflammatory responses
| PRJNA1095469 | ENA
Project description:The body-brain axis is emerging as a principal conductor of organismal physiology. It senses and controls organ function, metabolism and nutritional state. Here, we show that a peripheral immune insult powerfully activates the body-brain axis to regulate immune responses. We demonstrate that pro- and anti-inflammatory cytokines communicate with distinct populations of vagal neurons to inform the brain of an emerging inflammatory response. In turn, the brain tightly modulates the course of the peripheral immune response. Genetic silencing of this body-to-brain circuit produced unregulated and out-of-control inflammatory responses. By contrast, activating, rather than silencing, this circuit affords exceptional neural control of immune responses. We used single-cell RNA sequencing, combined with functional imaging, to identify the circuit components of this neuro-immune axis, and showed that its selective manipulation can effectively suppress the pro-inflammatory response while enhancing an anti-inflammatory state. The brain-evoked transformation of the course of an immune response offers new possibilities in the modulation of a wide range of immune disorders, from autoimmune diseases to cytokine storm and shock.
2024-04-11 | GSE263025 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE36241: Identification of a FOXO3/IRF7 circuit that limits inflammatory sequelae of antiviral responses (ChIP-Seq) GSE37051: Identification of a FOXO3/IRF7 circuit that limits inflammatory sequelae of antiviral responses (expression) Refer to individual Series
2012-09-19 | E-GEOD-37052 | biostudies-arrayexpress
Project description:Inflammation is characterized by a biphasic cycle consisting initially of a pro-inflammatory phase which is subsequently resolved by anti-inflammatory processes. The coordination of these two disparate states needs to be highly controlled, suggesting that the regulation of the cytokines that drive these processes are intimately linked. Interleukin-1 beta (IL1B) is a master regulator of pro-inflammation and is encoded within the same topologically associated domain (TAD) as interleukin-37 (IL37). IL37 has recently emerged as a powerful anti-inflammatory cytokine which diametrically opposes the function of IL1B. Within this TAD, we identified a novel long non-coding RNA called AMANZI which negatively regulates IL1B expression and trained immunity through the induction of IL37 transcription. We found that the activation of IL37 occurs through the formation of a dynamic long-range chromatin contact that leads to the temporal delay of anti-inflammatory responses. The common variant rs16944 present in AMANZI augments this regulatory circuit, predisposing individuals to enhanced pro-inflammation or immunosuppression. Our work illuminates a chromatin-mediated biphasic circuit coordinating expression of IL1B and IL37, thereby regulating two functionally opposed states of inflammation from within a single TAD.
2023-10-27 | PXD045971 | Pride
Project description:A gut-brain-body circuit mediates immune evasion in viral infection
| PRJNA1212042 | ENA
Project description:Innate immune cells including myeloid cells exhibit dynamic cellular switches during inflammatory and immune responses against infection. These processes are tightly regulated at different levels including the cis-regulatory elements of immune cells. However, it remains unclear how the dynamic states of cis-regulatory elements of innate immune cells are controlled during inflammatory responses. Here we found that histone methylation regulator PTIP orchestrates inflammatory responses of macrophages through regulating acetylation state of enhancers and promoters. Rapid elevated expression of PTIP is observed in primary human and mouse macrophages upon lipopolysaccharide (LPS) stimulation. Loss of PTIP represses transcription of pro-inflammatory genes, and activates expression of anti-inflammatory genes. Mechanistically, we found that, independent of its function in histone methylation, PTIP interacts with acetyltransferase p300 and deacetylase HDACs, and serves as a beacon to recruit them to specific sites of inflammatory genes respectively. PTIP deficiency alters H3K27 acetylation state of cis-regulatory elements of inflammatory genes. Moreover, PTIP and c-JUN shape a positive and feedforward regulatory circuit. In addition, PTIP deletion sustains immunosuppressive function of tumor-associated macrophages (TAMs) and promotes tumor growth. Overall, our findings uncover a critical role of PTIP in altering the acetylation state of cis-regulatory regions and fine-tuning the inflammatory responses of innate immune cells.
2022-12-30 | GSE163463 | GEO
Project description:Invasive candidiasis is a serious healthcare problem with high mortality rates, particularly in immunocompromised patients. Understanding how the immune response towards Candida albicans is mounted and controlled is fundamental to developing new therapeutic strategies. Protein tyrosine phosphatase 1B (PTP1B) is a key phosphatase regulating various immunoreceptor signalling cascades including inflammatory and metabolic responses and a pharmaceutical target. This study uncovers the importance of PTP1B in driving protective antifungal immune cell responses post-infection. Following systemic C. albicans infection, mice lacking PTP1B in myeloid cells (LysM PTP1B-/-) were significantly more susceptible to infection, with lower survival rates, greater body weight loss and higher fungal burdens in brain, kidney, and liver. LysM PTP1B-/- infected mice exhibited increased expression of organ inflammatory cytokines TNF, IL-10, IL-6 and IL-1β and increased kidney tubular inflammation, 1- and 3-days post-infection. Kidneys from infected LysM PTP1B-/- mice also demonstrated significantly increased chemokine expression and leukocyte infiltration, collectively promoting immunopathology. PTP1B-/- neutrophils infiltrating into kidneys were, however, less mature and in vitro produced less ROS. Bone marrow-derived macrophages from LysM PTP1B-/- mice, through proteomic analysis, show enhancement of immune response and type I interferon signalling pathways, and they were less able to phagocytose and kill C. albicans relating to changes in their metabolism and viability when fighting infection. The decrease in phagocytosis and viability in PTP1B-/- macrophages following infection translated to human macrophages treated with a pharmacological PTP1B inhibitor. Our data provides new insights connecting the critical role of myeloid cell PTP1B in regulating immune defence against C. albicans through modulating levels of inflammatory cytokines, neutrophil clearance mechanisms and macrophage functional and metabolic responses, implying that boosting specific PTP1B-dependent signalling pathways could have therapeutic implications for combatting systemic fungal infection.
2025-08-28 | PXD057300 | Pride
Project description:Innate immune cells including myeloid cells exhibit dynamic cellular switches during inflammatory and immune responses against infection. These processes are tightly regulated at different levels including the cis-regulatory elements of immune cells. However, it remains unclear how the dynamic states of cis-regulatory elements of innate immune cells are controlled during inflammatory responses. Here we found that histone methylation regulator PTIP orchestrates inflammatory responses of macrophages through regulating acetylation state of enhancers and promoters. Rapid elevated expression of PTIP is observed in primary human and mouse macrophages upon lipopolysaccharide (LPS) stimulation. Loss of PTIP represses transcription of pro-inflammatory genes, and activates expression of anti-inflammatory genes. Mechanistically, we found that, independent of its function in histone methylation, PTIP interacts with acetyltransferase p300 and deacetylase HDACs, and serves as a beacon to recruit them to specific sites of inflammatory genes respectively. PTIP deficiency alters H3K27 acetylation state of cis-regulatory elements of inflammatory genes. Moreover, PTIP and c-JUN shape a positive and feedforward regulatory circuit. In addition, PTIP deletion sustains immunosuppressive function of tumor-associated macrophages (TAMs) and promotes tumor growth. Overall, our findings uncover a critical role of PTIP in altering the acetylation state of cis-regulatory regions and fine-tuning the inflammatory responses of innate immune cells.
2022-12-30 | GSE163221 | GEO
Project description:Innate immune cells including myeloid cells exhibit dynamic cellular switches during inflammatory and immune responses against infection. These processes are tightly regulated at different levels including the cis-regulatory elements of immune cells. However, it remains unclear how the dynamic states of cis-regulatory elements of innate immune cells are controlled during inflammatory responses. Here we found that histone methylation regulator PTIP orchestrates inflammatory responses of macrophages through regulating acetylation state of enhancers and promoters. Rapid elevated expression of PTIP is observed in primary human and mouse macrophages upon lipopolysaccharide (LPS) stimulation. Loss of PTIP represses transcription of pro-inflammatory genes, and activates expression of anti-inflammatory genes. Mechanistically, we found that, independent of its function in histone methylation, PTIP interacts with acetyltransferase p300 and deacetylase HDACs, and serves as a beacon to recruit them to specific sites of inflammatory genes respectively. PTIP deficiency alters H3K27 acetylation state of cis-regulatory elements of inflammatory genes. Moreover, PTIP and c-JUN shape a positive and feedforward regulatory circuit. In addition, PTIP deletion sustains immunosuppressive function of tumor-associated macrophages (TAMs) and promotes tumor growth. Overall, our findings uncover a critical role of PTIP in altering the acetylation state of cis-regulatory regions and fine-tuning the inflammatory responses of innate immune cells.
2022-12-30 | GSE163208 | GEO