Project description:Dysfunction of group II innate lymphoid cells (ILC2s) plays an important role in the development of type II inflammation-related diseases such as asthma and pulmonary fibrosis. Notably, neural signals are increasingly recognized as pivotal regulators of ILC2s. However, how ILC2s intrinsically modulate their responsiveness to these neural signals is still largely unknown. Here, using single-cell RNA sequencing and bulk mRNA sequencing, we report that the immune regulatory molecule PAC1 (phosphatase of activated cells 1) selectively promotes the signaling of neuropeptide CGRP (calcitonin gene-related peptide) in ILC2s. Moreover, PAC1 is necessary for ensuring the expression of CGRP-response genes by influencing chromatin accessibility. In summary, our study demonstrates that PAC1 is an important regulator of ILC2 responses and we propose that PAC1 is a potential target for therapeutic interventions of type II inflammation-related diseases.
Project description:Dysfunction of group II innate lymphoid cells (ILC2s) plays an important role in the development of type II inflammation-related diseases such as asthma and pulmonary fibrosis. Notably, neural signals are increasingly recognized as pivotal regulators of ILC2s. However, how ILC2s intrinsically modulate their responsiveness to these neural signals is still largely unknown. Here, using single-cell RNA sequencing and bulk mRNA sequencing, we report that the immune regulatory molecule PAC1 (phosphatase of activated cells 1) selectively promotes the signaling of neuropeptide CGRP (calcitonin gene-related peptide) in ILC2s. Moreover, PAC1 is necessary for ensuring the expression of CGRP-response genes by influencing chromatin accessibility. In summary, our study demonstrates that PAC1 is an important regulator of ILC2 responses and we propose that PAC1 is a potential target for therapeutic interventions of type II inflammation-related diseases.
Project description:Dysfunction of group II innate lymphoid cells (ILC2s) plays an important role in the development of type II inflammation-related diseases such as asthma and pulmonary fibrosis. Notably, neural signals are increasingly recognized as pivotal regulators of ILC2s. However, how ILC2s intrinsically modulate their responsiveness to these neural signals is still largely unknown. Here, using single-cell RNA sequencing and bulk mRNA sequencing, we report that the immune regulatory molecule PAC1 (phosphatase of activated cells 1) selectively promotes the signaling of neuropeptide CGRP (calcitonin gene-related peptide) in ILC2s. Moreover, PAC1 is necessary for ensuring the expression of CGRP-response genes by influencing chromatin accessibility. In summary, our study demonstrates that PAC1 is an important regulator of ILC2 responses and we propose that PAC1 is a potential target for therapeutic interventions of type II inflammation-related diseases.
Project description:LPS-stimulated macrophages from Pac1+/+ and Pac1-/- mice were compared to assess gene expression changes in the absence of PAC-1 (also known as Dual specificity phosphatase 2). Keywords: Comparison of Pac1+/+ with Pac1-/- activated macrophages
Project description:LPS-stimulated macrophages from Pac1+/+ and Pac1-/- mice were compared to assess gene expression changes in the absence of PAC-1 (also known as Dual specificity phosphatase 2). Experiment Overall Design: Age matched Pac1+/+ and Pac1-/- littermates were used to obtain equal numbers of thiolycollate-elicited macrophages. Pure populations of macrophages were stimulated with 100 ng/ml of LPS for 6 hours. 6 hours was chosen to assess mainly inflammatory gene expression.
Project description:Type 2 inflammation contributes to the pathology of skin diseases such as atopic dermatitis and urticaria. Type 2 innate lymphoid cells are key mediators of skin inflammation by releasing type 2 cytokines in response to certain environmental stimuli. We recently found that Rag1 knockout mice exhibit more pronounced skin inflammation in a mouse model of atopic-dermatitis-like disease, despite lacking adaptive immune cells like T helper 2 cells, implicating a critical role of type 2 innate lymphoid cells in this condition. The goal of this study was to characterize transcriptional differences between WT and Rag KO type 2 innate lymphoid cells to determine if Rag knockout leads to cell-intrinsic alterations in innate lymphoid cell function.
Project description:To analyze the effects of PAC1 on acetylation of H3K27 in exhausted CD8+ T cells, we isolated CD8+ T cells from spleen of wild-type or PAC1-/- mice post LCMV Cl13 infection and performed ChIP-seq with anti-H3K27-ac.