Inhibition of NFAT5-Dependent Astrocyte Swelling Alleviates Neuropathic Pain.

Astrocyte swelling is implicated in various neurological disorders. However, whether astrocyte swelling contributes to neuropathic pain remains elusive. This study elucidates the pivotal role of the nuclear factor of activated T-cells 5 (NFAT5) emerges as a master regulator of astrocyte swelling in the spinal dorsal horn (SDH) during neuropathic pain.

The arginine methyltransferase PRMT5 promotes mucosal defense in the intestine.

PRMT5 is a type II arginine methyltransferase abundantly expressed in the colonic epithelium. It is up-regulated in inflammatory bowel disease and colorectal cancer. However, its role in mucosal defense against enteric infection has not been studied.

The long non-coding RNA MALAT1 regulates intestine host-microbe interactions and polyposis.

The long non-coding RNA (lncRNA) Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) maintains the integrity of the intestinal epithelial barrier and regulates local inflammation. However, its influences on intestinal microbial communities and tissue susceptibility to cancer development remain unexplored. Here, we report that MALAT1 regulates host anti-microbial response gene expression and the composition of mucosal-associated microbial communities in a region-specific manner.

Regulation of CD8 T Cell Differentiation by the RNA-Binding Protein DDX5.

The RNA-binding protein DEAD-box protein 5 (DDX5) is a polyfunctional regulator of gene expression, but its role in CD8+ T cell biology has not been extensively investigated. In this study, we demonstrate that deletion of DDX5 in murine CD8+ T cells reduced the differentiation of terminal effector, effector memory T, and terminal effector memory cells while increasing the generation of central memory T cells, whereas forced expression of DDX5 elicited the opposite phenotype. DDX5-deficient CD8+ T cells exhibited increased expression of genes that promote central memory T cell differentiation, including Tcf7 and Eomes.

Candida albicans-specific Th17 cell-mediated response contributes to alcohol-associated liver disease.

Alcohol-associated liver disease is accompanied by intestinal mycobiome dysbiosis, yet the impacts on liver disease are unclear. We demonstrate that Candida albicans-specific T helper 17 (Th17) cells are increased in circulation and present in the liver of patients with alcohol-associated liver disease. Chronic ethanol administration in mice causes migration of Candida albicans (C.

RNA binding protein DDX5 restricts RORγt T suppressor function to promote intestine inflammation.

Retinoid-related orphan receptor (RAR) gamma (RORγt)-expressing regulatory T cells (RORγt T) play pivotal roles in preventing T cell hyperactivation and maintaining tissue homeostasis, in part by secreting the anti-inflammation cytokine interleukin-10 (IL-10). Here, we report that hypoxia-induced factor 1α (HIF1α) is the master transcription factor for in RORγt T. This critical anti-inflammatory pathway is negatively regulated by an RNA binding protein DEAD box helicase 5 (DDX5).

Protocol to assess cell-intrinsic regulatory mechanisms using an ex vivo murine T cell polarization and co-culture system.

This protocol describes an ex vivo cell culture system for simultaneously generating a mixture of CD4 T helper lineages, including T helper 17 (Th17), RORγt Treg, and conventional Treg (cTreg), in proportions representative of those found in mucosal tissues in vivo. When combined with a co-culture approach, this system allows a more rapid assessment of a candidate molecule's T cell-intrinsic and -extrinsic functions over the traditional bone marrow chimera and co-transfer approaches. For complete details on the use and execution of this protocol, please refer to Ma et al.

RORγt phosphorylation protects against T cell-mediated inflammation.

RAR-related orphan receptor-γ (RORγt) is an essential transcription factor for thymic T cell development, secondary lymphoid tissue organogenesis, and peripheral immune cell differentiation. Serine 182 phosphorylation is a major post-translational modification (PTM) on RORγt. However, the in vivo contribution of this PTM in health and disease settings is unclear.

RNA binding protein DDX5 directs tuft cell specification and function to regulate microbial repertoire and disease susceptibility in the intestine.

Objective: Tuft cells residing in the intestinal epithelium have diverse functions. In the small intestine, they provide protection against inflammation, combat against helminth and protist infections, and serve as entry portals for enteroviruses. In the colon, they had been implicated in tumourigenesis.

The DNA Glycosylase NEIL2 Suppresses -Infection-Induced Inflammation and DNA Damage in Colonic Epithelial Cells.

Colorectal cancer (CRC) is the third most prevalent cancer, while the majority (80-85%) of CRCs are sporadic and are microsatellite stable (MSS), and approximately 15-20% of them display microsatellite instability (MSI). Infection and chronic inflammation are known to induce DNA damage in host tissues and can lead to oncogenic transformation of cells, but the role of DNA repair proteins in microbe-associated CRCs remains unknown. Using CRC-associated microbes such as () in a coculture with murine and human enteroid-derived monolayers (EDMs), here, we show that, among all the key DNA repair proteins, NEIL2, an oxidized base-specific DNA glycosylase, is significantly downregulated after infection.

DDX5 promotes oncogene C3 and FABP1 expressions and drives intestinal inflammation and tumorigenesis.

Tumorigenesis in different segments of the intestinal tract involves tissue-specific oncogenic drivers. In the colon, complement component 3 (C3) activation is a major contributor to inflammation and malignancies. By contrast, tumorigenesis in the small intestine involves fatty acid-binding protein 1 (FABP1).

Noncoding RNAs in inflammation and colorectal cancer.

Despite advanced clinical treatments, mortality in patients with metastatic colorectal cancer (CRC) remains high. Three critical determinants in CRC progression include the epithelial proliferation checkpoints, epithelial-to-mesenchymal transition (EMT) and inflammatory cytokines in the tumour microenvironment. Genes involved in these three processes are regulated at the transcriptional and post-transcriptional level.