Synovial regulatory T cells expressing ST2 deteriorate joint inflammation through the suppression of immunoregulatory eosinophils.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic polyarthritis. It is well-established that helper T cells play crucial roles in the development and deterioration of RA. Recent studies also revealed the significant roles of regulatory T (Treg) cells in this context.

Stage-specific GATA3 induction promotes ILC2 development after lineage commitment.

Group 2 innate lymphoid cells (ILC2s) are a subset of innate lymphocytes that produce type 2 cytokines, including IL-4, IL-5, and IL-13. GATA3 is a critical transcription factor for ILC2 development at multiple stages. However, when and how GATA3 is induced to the levels required for ILC2 development remains unclear.

A distal enhancer of GATA3 regulates Th2 differentiation and allergic inflammation.

Asthma is a widespread airway disorder where GATA3-dependent Type-2 helper T (Th2) cells and group 2 innate lymphoid cells (ILC2s) play vital roles. Asthma-associated single nucleotide polymorphisms (SNPs) are enriched in a region located 926-970 kb downstream from GATA3 in the 10p14 (hG900). However, it is unknown how hG900 affects the pathogenesis of allergic airway inflammation.

Physiological and immunological barriers in the lung.

The lungs serve as the primary organ for respiration, facilitating the vital exchange of gases with the bloodstream. Given their perpetual exposure to external particulates and pathogens, they possess intricate protective barriers. Cellular adhesion in the lungs is robustly maintained through tight junctions, adherens junctions, and desmosomes.

IL-21 is required for the maintenance and pathogenesis of murine Vγ4 IL-17-producing γδT cells.

Murine IL-17-producing γδT (γδT17) cells are divided into two subsets: natural γδT17 (nγδT17) cells, whose development is restricted to the fetal thymus, and inducible γδT17 cells, which require antigen exposure for their IL-17 production and are presumed to develop from immature γδT17 cells in the adult thymus and whose T cell receptor (TCR) is biased toward Vγ4. Although IL-23 is known to be involved in developing γδT17 cells, the roles of other cytokines, such as IL-21, which is involved in developing Th17 cells like IL-23, in the development, maintenance, and pathophysiology of γδT17 cells remain unknown. Here, we show that IL-21 is dispensable for the fetal thymic development of nγδT17 cells but is required for the peripheral maintenance of Vγ4nγδT17 cells.

CCR4 predicts the efficacy of abatacept in rheumatoid arthritis patients through the estimation of Th17 and Treg cell abundance.

Objectives: Predicting the efficacy of biological disease-modifying antirheumatic drugs is challenging. In this study, we aimed to explore markers that predict the efficacy of abatacept in rheumatoid arthritis (RA) patients.

Methods: Thirty RA patients receiving abatacept were recruited, and peripheral blood mononuclear cells from the participants were subjected to DNA microarray analysis.

TAp63, a methotrexate target in CD4+ T cells, suppresses Foxp3 expression and exacerbates autoimmune arthritis.

Methotrexate (MTX) is a standard, first-line therapy for rheumatoid arthritis (RA); however, its precise mechanisms of action other than antifolate activity are largely unknown. We performed DNA microarray analyses of CD4+ T cells in patients with RA before and after MTX treatment and found that TP63 was the most significantly downregulated gene after MTX treatment. TAp63, an isoform of TP63, was highly expressed in human IL-17-producing Th (Th17) cells and was suppressed by MTX in vitro.

A role of Achaete-scute complex homolog 2 in T follicular regulatory cell development.

T follicular regulatory (Tfr) cells, a subset of CD4 Foxp3 regulatory T (Treg) cells, locate to the lymphoid follicle and germinal center (GC) and regulate antibody responses. Tfr cells express the functional molecules of follicular helper T (Tfh) cells, including CXCR5 and Bcl6. CD25 mature Tfr cells differentiate from CD25 Treg cells through CD25 immature Tfr cells.

Upconversion time-stretch infrared spectroscopy.

High-speed measurement confronts the extreme speed limit when the signal becomes comparable to the noise level. In the context of broadband mid-infrared spectroscopy, state-of-the-art ultrafast Fourier-transform infrared spectrometers, in particular dual-comb spectrometers, have improved the measurement rate up to a few MSpectra s, which is limited by the signal-to-noise ratio. Time-stretch infrared spectroscopy, an emerging ultrafast frequency-swept mid-infrared spectroscopy technique, has shown a record-high rate of 80 MSpectra s with an intrinsically higher signal-to-noise ratio than Fourier-transform spectroscopy by more than the square-root of the number of spectral elements.

Epithelial cell-derived cytokine TSLP activates regulatory T cells by enhancing fatty acid uptake.

Epithelial cells control a variety of immune cells by secreting cytokines to maintain tissue homeostasis on mucosal surfaces. Regulatory T (Treg) cells are essential for immune homeostasis and for preventing tissue inflammation; however, the precise molecular mechanisms by which epithelial cell-derived cytokines function on Treg cells in the epithelial tissues are not well understood. Here, we show that peripheral Treg cells preferentially respond to thymic stromal lymphoprotein (TSLP).

Loss of SLC26A3 Results in Colonic Mucosal Immune Dysregulation via Epithelial-Immune Cell Crosstalk.

Background & Aims: Down-regulation of chloride transporter SLC26A3 or down-regulated in adenoma (DRA) in colonocytes has recently been linked to the pathogenesis of ulcerative colitis (UC). Because exaggerated immune responses are one of the hallmarks of UC, these current studies were undertaken to define the mechanisms by which loss of DRA relays signals to immune cells to increase susceptibility to inflammation.

Methods: NanoString Immunology Panel, fluorescence assisted cell sorting, immunoblotting, immunofluorescence, and quantitative real-time polymerase chain reaction assays were used in wild-type and DRA knockout (KO) mice.

Detecting time-evolving phenotypic components of adverse reactions against BNT162b2 SARS-CoV-2 vaccine via non-negative tensor factorization.

Symptoms of adverse reactions to vaccines evolve over time, but traditional studies have focused only on the frequency and intensity of symptoms. Here, we attempt to extract the dynamic changes in vaccine adverse reaction symptoms as a small number of interpretable components by using non-negative tensor factorization. We recruited healthcare workers who received two doses of the BNT162b2 mRNA COVID-19 vaccine at Chiba University Hospital and collected information on adverse reactions using a smartphone/web-based platform.

Rapid and quantitative detection of multiple antibodies against SARS-CoV-2 mutant proteins by photo-immobilized microarray.

A rapid automatic quantitative diagnostic system for multiple SARS-CoV-2 mutant protein-specific antibodies was developed using a microarray with photoreactive polymers. Two types of photoreactive polymers, phenylazide and polyoxyethylene, were prepared. The polymers were coated on a plastic plate.

Antibody responses and SARS-CoV-2 infection after BNT162b2 mRNA booster vaccination among healthcare workers in Japan.

Introduction: Vaccine effectiveness against SARS-CoV-2 infections decreases due to waning immunity, and booster vaccination was therefore introduced. We estimated the anti-spike antibody (AS-ab) recovery by booster vaccination and analyzed the risk factors for SARS-CoV-2 infections.

Methods: The subjects were health care workers (HCWs) in a Chiba University Hospital vaccination cohort.

Airway epithelial STAT3 inhibits allergic inflammation via upregulation of stearoyl-CoA desaturase 1.

Background: Airway epithelial cells (AECs) play a crucial role in the induction and development of allergic inflammation through the development and activation of immune cells, including Th2 cells and ILC2s. Recent studies have revealed that STAT3 expressed in epithelial cells protects against pathogens and maintains homeostasis in the intestine. However, the roles of STAT3 in airway epithelium are poorly understood.

Markers of Memory CD8 T Cells Depicting the Effect of the BNT162b2 mRNA COVID-19 Vaccine in Japan.

BNT162b2, a nucleoside-modified mRNA vaccine for SARS-CoV-2 spike glycoprotein (S), provides approximately 95% efficacy for preventing COVID-19. However, it remains unclear how effectively memory CD8+ T cells are generated and which genetic and environmental factors affect the generation and function of memory CD8+ T cells elicited by this vaccine. Here, we investigated the frequency and functions of memory CD8+ T cells 3 weeks after the second vaccination in the Japanese population.

Immunological features that associate with the strength of antibody responses to BNT162b2 mRNA vaccine against SARS-CoV-2.

Predictive clinical factors associated with favorable responses to BNT162b2 mRNA vaccine against SARS-CoV-2 have been reported in some studies; however, there is a subgroup with low antibodytiters without well-known clinical factors reducing antibody responses. To clarify the immunological backgrounds that underlie the difference in antibody responses, we analyzed peripheral blood mononuclear cells (PBMCs) of each 20 individuals with a high anti-SARS-CoV-2 antibody titer and a low antibody titer out of 1774 healthcare workers who received BNT162b2 mRNA vaccine. A higher percentage of B cells before vaccination was associated with a higher antibody titer.

NF-κB1 Contributes to Imiquimod-Induced Psoriasis-Like Skin Inflammation by Inducing Vγ4Vδ4γδT17 Cells.

Recent studies have identified NF-κB1 as a new disease susceptibility gene for psoriasis. Although accumulating evidence has shown the importance of NF-κB signaling in various cell types in the pathogenesis of psoriasis, it remains unclear how NF-κB1 contributes to the pathogenesis of psoriasis. In this study, we examined psoriasis-like skin diseases induced by topical administration of imiquimod in Nf-κb1‒deficient (Nf-κb1) mice and littermate wild-type (WT) mice.

Redundant cytokine requirement for intestinal microbiota-induced Th17 cell differentiation in draining lymph nodes.

Differentiation of intestinal T helper 17 (Th17) cells, which contribute to mucosal barrier protection from invasive pathogens, is dependent on colonization with distinct commensal bacteria. Segmented filamentous bacteria (SFB) are sufficient to support Th17 cell differentiation in mouse, but the molecular and cellular requirements for this process remain incompletely characterized. Here, we show that intestine-draining mesenteric lymph nodes (MLNs), not intestine proper, are the dominant site of SFB-induced intestinal Th17 cell differentiation.

Antibody responses to BNT162b2 mRNA COVID-19 vaccine and their predictors among healthcare workers in a tertiary referral hospital in Japan.

Objectives: This study aimed to determine antibody responses in healthcare workers who receive the BNT162b2 mRNA COVID-19 vaccine and identify factors that predict the response.

Methods: We recruited healthcare workers receiving the BNT162b2 mRNA COVID-19 vaccine at the Chiba University Hospital COVID-19 Vaccine Center. Blood samples were obtained before the 1st dose and after the 2nd dose vaccination, and serum antibody titers were determined using Elecsys® Anti-SARS-CoV-2S, an electrochemiluminescence immunoassay.

Compressive dual-comb spectroscopy.

Broadband, high resolution, and rapid measurements of dual-comb spectroscopy (DCS) generate a large amount of data stream. We numerically demonstrate significant data compression of DCS spectra by using a compressive sensing technique. Our numerical simulation shows a compression rate of more than 100 with a 3% error in mole fraction estimation of mid-infrared (MIR) DCS of two molecular species in a broadband (~ 30 THz) and high resolution (~ 115 MHz) condition.