Roseburia intestinalis-derived butyrate alleviates neuropathic pain.

Approximately 20% of patients with shingles develop postherpetic neuralgia (PHN). We investigated the role of gut microbiota in shingle- and PHN-related pain. Patients with shingles or PHN exhibited significant alterations in their gut microbiota with microbial markers predicting PHN development among patients with shingles.

Sodium butyrate restored TRESK current controlling neuronal hyperexcitability in a mouse model of oxaliplatin-induced peripheral neuropathic pain.

Chemotherapy-induced peripheral neuropathy (CIPN) and its related pain are common challenges for patients receiving oxaliplatin chemotherapy. Oxaliplatin accumulation in dorsal root ganglion (DRGs) is known to impair gene transcription by epigenetic dysregulation. We hypothesized that sodium butyrate, a pro-resolution short-chain fatty acid, inhibited histone acetylation in DRGs and abolished K channel dysregulation-induced neuronal hyperexcitability after oxaliplatin treatment.

Expansion of memory Vδ2 T cells following SARS-CoV-2 vaccination revealed by temporal single-cell transcriptomics.

γδ T cells provide rapid cellular immunity against pathogens. Here, we conducted matched single-cell RNA-sequencing and γδ-TCR-sequencing to delineate the molecular changes in γδ T cells during a longitudinal study following mRNA SARS-CoV-2 vaccination. While the first dose of vaccine primes Vδ2 T cells, it is the second administration that significantly boosts their immune response.

A monoclonal Trd chain supports the development of the complete set of functional γδ T cell lineages.

The clonal selection theory describes key features of adaptive immune responses of B and T cells. For αβ T cells and B cells, antigen recognition and selection principles are known at a detailed molecular level. The precise role of the antigen receptor in γδ T cells remains less well understood.

Corrigendum: Systematic pattern analyses of Vδ2 TCRs reveal that shared "public" Vδ2 γδ T cell clones are a consequence of rearrangement bias and a higher expansion status.

[This corrects the article DOI: 10.3389/fimmu.2022.

Systematic pattern analyses of Vδ2 TCRs reveal that shared "public" Vδ2 γδ T cell clones are a consequence of rearrangement bias and a higher expansion status.

Background: Vγ9Vδ2 T cells are a major innate T cell subset in human peripheral blood. Their Vδ2 VDJ-rearrangements are short and simple in the fetal thymus and gradually increase in diversity and CDR3 length along with development. So-called "public" versions of Vδ2 TCRs are shared among individuals of all ages.

A CMV-induced adaptive human Vδ1+ γδ T cell clone recognizes HLA-DR.

The innate and adaptive roles of γδ T cells and their clonal γδ T cell receptors (TCRs) in immune responses are still unclear. Recent studies of γδ TCR repertoire dynamics showed massive expansion of individual Vδ1+ γδ T cell clones during viral infection. To judge whether such expansion is random or actually represents TCR-dependent adaptive immune responses, information about their cognate TCR ligands is required.

Dopamine Signaling Promotes Tissue-Resident Memory Differentiation of CD8+ T Cells and Antitumor Immunity.

Unlabelled: Tissue-resident memory CD8+ T (TRM) cells have been associated with robust protective antitumor immune responses and improved prognosis of patients with cancer. Therefore, therapeutic strategies that modulate either the production or activity of TRM cells could be effective for treating cancer. Using a high-throughput drug screen, we showed that the neurotransmitter dopamine drives differentiation of CD8+ T cells into CD103+ TRM cells.

γδ T cells license immature B cells to produce a broad range of polyreactive antibodies.

Immature autoreactive B cells are present in all healthy individuals, but it is unclear which signals are required for their maturation into antibody-producing cells. Inducible depletion of γδ T cells show that direct interaction between γδ T cells and immature B cells in the spleen support an "innate" transition to mature B cells with a broad range of antigen specificities. IL-4 production of γδ T cells and cell-to-cell contact via CD30L support B cell maturation and induce genes of the unfolded protein response and mTORC1 signaling.

NKG2A expression identifies a subset of human Vδ2 T cells exerting the highest antitumor effector functions.

Human Vδ2 cells are innate-like γδ T effectors performing potent immune surveillance against tumors. The constitutive expression of NKG2A identifies a subset of Vδ2 T cells licensed with an intrinsic hyper-responsiveness against cancer. Indeed, the transcriptomic profiles of NKG2A and NKG2A cells characterize two distinct "intralineages" of Vδ2 T lymphocytes that appear early during development, keep their phenotypes, and show self-renewal capabilities in adult life.

Generation of hiPSC-derived low threshold mechanoreceptors containing axonal termini resembling bulbous sensory nerve endings and expressing Piezo1 and Piezo2.

Somatosensory low threshold mechanoreceptors (LTMRs) sense innocuous mechanical forces, largely through specialized axon termini termed sensory nerve endings, where the mechanotransduction process initiates upon activation of mechanotransducers. In humans, a subset of sensory nerve endings is enlarged, forming bulb-like expansions, termed bulbous nerve endings. There is no in vitro human model to study these neuronal endings.

Clonal expansion of CD8+ T cells reflects graft-versus-leukemia activity and precedes durable remission following DLI.

Donor lymphocyte infusion (DLI) is a standard of care for relapse of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Currently it is poorly understood how and when CD8+ αβ T cells exert graft-versus-leukemia (GVL) activity after DLI. Also, there is no reliable biomarker to monitor GVL activity of the infused CD8+ T cells.

A fetal wave of human type 3 effector γδ cells with restricted TCR diversity persists into adulthood.

Accumulating evidence suggests that the mouse embryonic thymus produces distinct waves of innate effector γδ T cells. However, it is unclear whether this process occurs similarly in humans and whether it comprises a dedicated subset of innate-like type 3 effector γδ T cells. Here, we present a protocol for high-throughput sequencing of and pairs that comprise the clonal γδTCR.

Amino acids and RagD potentiate mTORC1 activation in CD8 T cells to confer antitumor immunity.

Background: In the tumor microenvironment, tumor cells are able to suppress antitumor immunity by competing for essential nutrients, including amino acids. However, whether amino acid depletion modulates the activity of CD8 tumor-infiltrating lymphocytes (TILs) is unclear.

Method: In this study, we evaluated the roles of amino acids and the Rag complex in regulating mammalian target of rapamycin complex 1 (mTORC1) signaling in CD8 TILs.

TCR repertoire analysis reveals phosphoantigen-induced polyclonal proliferation of Vγ9Vδ2 T cells in neonates and adults.

The Vγ9Vδ2 T cell subset is the major γδ T cell subset in human peripheral blood and has the unique ability to contribute to immune surveillance by detecting pyrophosphorylated metabolites of isoprenoid synthesis, termed phosphoantigens (pAgs). Vγ9Vδ2 T cells are first detected at midgestation and show postnatal expansion. Interestingly, neonatal Vγ9Vδ2 T cells display a higher TCR repertoire diversity with more public clonotypes and lower pAg responsiveness than in adults.

B cell hyperactivation in an Ackr4-deficient mouse strain is not caused by lack of ACKR4 expression.

The majority of genetically modified C57BL/6 mice contain congenic passenger DNA around the targeted gene locus as they were generated from 129-derived embryonic stem cells (ESCs) with subsequent backcrossing to the C57BL/6 genetic background. When studying the role of atypical chemokine receptor 4 (ACKR4) in the immune system, we realized that the two available Ackr4-deficient mouse strains (Ackr4 and Ackr4 ) show profoundly different phenotypes: Compared to wild-type and Ackr4 mice, Ackr4 mice show a strong accumulation of plasma blasts in mesenteric lymph node and spleen as well as increased B cell proliferation after in vitro activation. This phenotype was maintained after further backcrossing to C57BL/6 mice and was even present in heterozygous Ackr4 animals, suggesting that a gene variant on the targeted chromosome might cause this phenotype.

Single-Cell Transcriptomics Identifies the Adaptation of Scart1 Vγ6 T Cells to Skin Residency as Activated Effector Cells.

IL-17-producing γδ T cells express oligoclonal Vγ4 and Vγ6 TCRs, mainly develop in the prenatal thymus, and later persist as long-lived self-renewing cells in all kinds of tissues. However, their exchange between tissues and the mechanisms of their tissue-specific adaptation remain poorly understood. Here, single-cell RNA-seq profiling identifies IL-17-producing Vγ6 T cells as a highly homogeneous Scart1 population in contrast to their Scart2 IL-17-producing Vγ4 T cell counterparts.

Genetic models reveal origin, persistence and non-redundant functions of IL-17-producing γδ T cells.

γδ T cells are highly conserved in jawed vertebrates, suggesting an essential role in the immune system. However, γδ T cell-deficient mice display surprisingly mild phenotypes. We hypothesized that the lack of γδ T cells in constitutive mice is functionally compensated by other lymphocytes taking over genuine γδ T cell functions.

Nonsteroidal Anti-inflammatory Drugs Potently Inhibit the Replication of Zika Viruses by Inducing the Degradation of AXL.

Zika virus (ZIKV) is genetically and biologically related to other family members and has disseminated to many countries. It is associated with severe consequences, including the abnormal development of the neural system in fetuses and neurological diseases in adults. Therefore, the development of anti-ZIKV drugs is of paramount importance.

Identification of a novel compound targeting the nuclear export of influenza A virus nucleoprotein.

Although antiviral drugs are available for the treatment of influenza infection, it is an urgent requirement to develop new antiviral drugs regarding the emergence of drug-resistant viruses. The nucleoprotein (NP) is conserved among all influenza A viruses (IAVs) and has no cellular equivalent. Therefore, NP is an ideal target for the development of new IAV inhibitors.

Characteristic amino acid changes of influenza A(H1N1)pdm09 virus PA protein enhance A(H7N9) viral polymerase activity.

Human coinfection with a novel H7N9 influenza virus and the 2009 pandemic A(H1N1) influenza virus, H1N1pdm09, has recently been reported in China. Because reassortment can occur during coinfection, it is necessary to clarify the effects of gene reassortment between these two viruses. Among the viral ribonucleoprotein complex (vRNP) genes, only the PA gene of H1N1pdm09 enhances the avian influenza viral polymerase activity.