Association between Gut Microbiota and Muscle Strength in Japanese General Population of the Iwaki Health Promotion Project.

The association between the gut microbiota and muscle strength has garnered attention in the context of mitigating muscle decline. However, many study subjects have been individuals with existing illnesses or the elderly only. This study aims to elucidate the association between the gut microbiota and muscle strength indicators using grip strength/BMI in a large-scale study of community residents. The mean age of men (n = 442) and women (n = 588) was 50.5 (15.3) and 51.2 (15.9) years, respectively. The muscle strength indicator used was grip/BMI. The association between total read count and genus-level gut microbiota and muscle strength was analyzed. The mean grip/BMI was 1.8 (0.3) for men and 1.2 (0.2) for women. The genus of the gut microbiota that showed an association in both sexes was Eggerthella (men: ß = 0.18, CI: 0.04-0.31, p = 0.009; women: ß = 0.07, CI: 0.00-0.12, p = 0.028). Blautia, Eggerthella and Faecalibacterium were found to be significantly associated with grip/BMI in both the multiple regression analysis and Spearman's correlation analysis after the multiple comparison adjustment. These results suggest that an increase in Blautia and Eggerthella, coupled with a decrease in Faecalibacterium, may contribute to muscle strengthening or the suppression of muscle weakness.

CD69 Signaling in Eosinophils Induces IL-10 Production and Apoptosis via the Erk1/2 and JNK Pathways, Respectively.

INTRODUCTION: Eosinophils contribute to the pathogenesis of allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis. We previously reported that human tissue eosinophils have high CD69 expression compared to blood eosinophils, and its expression is correlated with disease severity and the number of infiltrated eosinophils. However, biological CD69 signaling activity in eosinophils remains unclear. METHODS: CD69 expression on lung tissue eosinophils obtained from mice with ovalbumin-induced asthma was measured using flow cytometry. CD69 crosslinking was performed on eosinophils purified from the spleen of IL-5 transgenic mice to investigate CD69 signaling and its function in eosinophils. Then, qPCR, Western blot, enzyme-linked immunosorbent assay, and survival assay results were analyzed. RESULTS: Surface CD69 expression on lung tissue eosinophils in the asthma mice model was 2.91% ± 0.76%, whereas no expression was detected in the healthy group. CD69-expressed eosinophils intrinsically have an upregulation of IL-10 mRNA expression. Moreover, CD69 crosslinking induced further pronounced IL-10 production and apoptosis; these responses were mediated via the Erk1/2 and JNK pathways, respectively. CONCLUSIONS: Our results suggested that CD69+ eosinophils play an immunoregulator role in type 2 inflammation, whereas activated tissue eosinophils contribute to the pathogenesis of asthma.

Discovery of Novel 11-Membered Templates as Squalene Synthase Inhibitors.

Squalene synthase is one of the most promising pharmaceutical targets to treat hyperlipidemia. Inhibition of the squalene synthase causes a decrease in the hepatic cholesterol concentration. We have already reported the design and synthesis of highly potent benzhydrol-type squalene inhibitors. Although these templates showed unique and potent cyclic active conformations via intramolecular hydrogen bonds, the in vivo cholesterol-lowering efficacy was insufficient. We attempted to improve their potential as an orally active medicine. In our medicinal chemistry effort, cyclized 11-membered ring templates were acquired. The novel series of compounds exhibited potent squalene synthase inhibitory activity, and one of the derivatives, isomer A-(1S, 3R)-14i, showed plasma lipid-lowering efficacy in hamster and marmoset repeated-dose studies. Our findings provide valuable insights into the design and development of novel and unique 11-membered ring-type highly potent squalene synthase inhibitors.

Correction: Kanda et al. Body Compression Corrective Garment and Eating Behavioural Change for Weight Reduction: The Mutsu City Randomised Controlled Trial. Healthcare 2023, 11, 942.

In the original publication [...].

The Neutralization of the Eosinophil Peroxidase Antibody Accelerates Eosinophilic Mucin Decomposition.

Eosinophilic airway inflammation, complicated by bronchial asthma and eosinophilic chronic rhinosinusitis (ECRS), is difficult to treat. The disease may become refractory when eosinophilic mucin associated with eosinophil peroxidase (EPX) and autoantibodies fills in the paranasal sinus and small airway. This study investigated the functional role of an anti-EPX antibody in eosinophilic mucin of ECRS in eosinophilic airway inflammation. Eosinophilic mucin was obtained from patients with ECRS. The effects of the anti-EPX antibody on dsDNA release from eosinophils and eosinophilic mucin decomposition were evaluated. Immunofluorescence or enzyme-linked immunosorbent assays were performed to detect the anti-EPX antibody and its supernatant and serum levels in eosinophilic mucin, respectively. The serum levels of the anti-EPX antibody were positively correlated with sinus computed tomography score and fractionated exhaled nitrogen oxide. Patients with refractory ECRS had higher serum levels of the anti-EPX antibody than those without. However, dupilumab treatment decreased the serum levels of the anti-EPX antibody. Immunoglobulins (Igs) in the immunoprecipitate of mucin supernatants enhanced dsDNA release from eosinophils, whereas the neutralization of Igs against EPX stopped dsDNA release. Furthermore, EPX antibody neutralization accelerated mucin decomposition and restored corticosteroid sensitivity. Taken together, the anti-EPX antibody may be involved in the formulation of eosinophilic mucin and be used as a clinical marker and therapeutic target for intractable eosinophilic airway inflammation.

Body Compression Corrective Garment and Eating Behavioural Change for Weight Reduction: The Mutsu City Randomised Controlled Trial.

Affordable and accessible behaviour-based interventions that do not overwhelm or demoralise overweight/obese individuals are needed. Combining clothing with behaviour change techniques might be an option. This is because clothing is a social norm, and clothing and motivation for weight loss are associated with the common desire to look better. Therefore, we conducted a single-blind randomised controlled trial to examine the effect of an intervention that combined behaviour change techniques, including simplified goal setting and self-monitoring, with a body compression corrective garment (BCCG), which exerts continuous but minimal tactile pressure on the hips and abdomen. We enrolled healthy community-dwelling adults with a body mass index ≥ 25 kg/m2 and assigned 35 and 34 participants to the intervention and control groups, respectively. The reduction in body weight was 1.3 kg more in the intervention group than in the control group after the 12-week intervention period (p < 0.05, repeated-measures mixed model). In addition, eating behaviour and body appreciation showed significant improvement in the intervention group compared with the control group. Our newly developed intervention improved eating behaviour and body appreciation and reduced the body weight of overweight/obese participants. Wearing a BCCG seems to facilitate behavioural changes and lead to weight loss.

Inoculation of lymphocytes from young mice prevents progression of age-related hearing loss in a senescence-associated mouse model.

Despite the increase in age-related hearing loss (ARHL) prevalence owing to increased population aging, preventive measures against ARHL have not yet been established. The immune system becomes one of the most dysfunctional systems upon aging, and immunosenescence greatly affects homeostasis and promotes systemic aging along with chronic inflammation and oxidative stress. This study aimed to determine whether immuno-rejuvenation procedures can prevent ARHL and have clinical applications as well as to analyze the communication mechanisms between the systemic immune system and the cochlea using a murine model. Lymphocytes from young mice inhibited the progression of ARHL. The method of cryopreserving these lymphocytes and inoculating them at the onset of ARHL suggests their clinical application. Mice that were administered this treatment not only maintained auditory threshold but also avoided spinal ganglion degeneration, cellular immune aging, and nitric oxide production, which causes age-related tissue damage. These findings coincide with our previous strategies against immunosenescence and neuronal aging. Therefore, the manipulation of systemic immune function may contribute not only to the prevention of ARHL but also to the development of novel anti-aging clinical measures, paving the way to healthy longevity with preserved organ function.

Omalizumab is effective for a patient with pollen-food allergy syndrome who experienced intractable lip edema.

Pollen-food allergy syndrome (PFAS) is an immunoglobulin E (IgE)-mediated allergic reaction caused when patients with pollen allergy ingest food having cross-reactivity with pollen. To date, no effective treatment method for this has been established. Here we report the case of a patient with PFAS who experienced lip edema, causing difficulties in treatment. This report describes the case of a 12-year-old boy with perennial allergic rhinitis since the age of 8 years. After ingesting fresh fruits and raw vegetables at the age of 11 years, he started to experience lip edema repeatedly. Thus, the patient was referred to our department. Based on the results of serum antigen-specific IgE, prick-to-prick, and allergen component tests, he was diagnosed with PFAS. He has been instructed to avoid causative food. Furthermore, the treatment using an antihistamine and antileukotriene receptor antagonist was initiated for pollen allergy. Sublingual immunotherapy (SLIT) for Japanese cedar pollen was initiated because the patient experienced severe nasal allergy symptoms during the dispersal season of this pollen. These treatments alleviated the nasal symptoms; however, the lip edema persisted. Omalizumab administration improved the lip edema. The combination of SLIT and omalizumab may be an effective treatment option for patients with PFAS.

CCL4 Regulates Eosinophil Activation in Eosinophilic Airway Inflammation.

Eosinophilic chronic rhinosinusitis (ECRS) is a refractory airway disease accompanied by eosinophilic inflammation, the mechanisms of which are unknown. We recently found that CCL4/MIP-1ß-a specific ligand for CCR5 receptors-was implicated in eosinophil recruitment into the inflammatory site and was substantially released from activated eosinophils. Moreover, it was found in nasal polyps from patients with ECRS, primarily in epithelial cells. In the present study, the role of epithelial cell-derived CCL4 in eosinophil activation was investigated. First, CCL4 expression in nasal polyps from patients with ECRS as well as its role of CCL4 in eosinophilic airway inflammation were investigated in an in vivo model. Furthermore, the role of CCL4 in CD69 expression-a marker of activated eosinophils-as well as the signaling pathways involved in CCL4-mediated eosinophil activation were investigated. Notably, CCL4 expression, but not CCL5, CCL11, or CCL26, was found to be significantly increased in nasal polyps from patients with ECRS associated with eosinophil infiltration as well as in BEAS-2B cells co-incubated with eosinophils. In an OVA-induced allergic mouse model, CCL4 increased eosinophil accumulation in the nasal mucosa and the bronchoalveolar lavage (BALF). Moreover, we found that CD69 expression was upregulated in CCL4-stimulated eosinophils; similarly, phosphorylation of several kinases, including platelet-derived growth factor receptor (PDGFR)ß, SRC kinase family (Lck, Src, and Yes), and extracellular signal-regulated kinase (ERK), was upregulated. Further, CCR5, PDGFRß, and/or Src kinase inhibition partially restored CCL4-induced CD69 upregulation. Thus, CCL4, which is derived from airway epithelial cells, plays a role in the accumulation and activation of eosinophils at inflammatory sites. These findings may provide a novel therapeutic target for eosinophilic airway inflammation, such as ECRS.

Efficacy of Combination Therapy with Lenvatinib and Radioactive Iodine in Thyroid Cancer Preclinical Model.

Patients with differentiated thyroid cancer (DTC) usually have good prognosis, while those with advanced disease have poor clinical outcomes. This study aimed to investigate the antitumor effects of combination therapy with lenvatinib and 131I (CTLI) using three different types of DTC cell lines with different profiling of sodium iodide symporter (NIS) status. The radioiodine accumulation study revealed a significantly increased radioiodine uptake in K1-NIS cells after lenvatinib treatment, while there was almost no uptake in K1 and FTC-133 cells. However, lenvatinib administration before radioiodine treatment decreased radioiodine uptake of K1-NIS xenograft tumor in the in vivo imaging study. CTLI synergistically inhibited colony formation and DTC cell migration, especially in K1-NIS cells. Finally, 131I treatment followed by lenvatinib administration significantly inhibited tumor growth of the NIS-expressing thyroid cancer xenograft model. These results provide important clinical implications for the combined therapy that lenvatinib should be administered after 131I treatment to maximize the treatment efficacy. Our synergistic treatment effects by CTLI suggested its effectiveness for RAI-avid thyroid cancer, which retains NIS function. This potential combination therapy suggests a powerful and tolerable new therapeutic strategy for advanced thyroid cancer.

CCL4 Functions as a Biomarker of Type 2 Airway Inflammation.

Eosinophilic airway inflammatory disease is associated with bronchial asthma, with eosinophilic chronic rhinosinusitis (ECRS) typical of refractory type 2 airway inflammation. CCL4 produced at local inflammatory sites is involved in them via the accumulation and activation of type 2 inflammatory cells, including eosinophils. The detailed mechanism of CCL4 production remains unclear, and also the possibility it could function as a biomarker of type 2 airway inflammation remains unresolved. In this study, we evaluated CCL4 mRNA expression and production via the TSLP receptor (TSLPR) and toll-like receptors (TLRs) or proteinase-activated receptor-2 (PAR2) in BEAS-2B bronchial epithelial cells co-incubated with purified eosinophils or eosinophil peroxidase (EPX). We examined serum chemokine (CCL4, CCL11, CCL26, and CCL17) and total IgE serum levels, fractionated exhaled nitrogen oxide (FENO), and CCL4 expression in nasal polyps in patients with severe ECRS and asthma. CCL4 was induced by TSLP under eosinophilic inflammation. Furthermore, CCL4 was released via TLR3 signaling, which was enhanced by TSLP. CCL4 was mainly located in nasal polyp epithelial cells, while serum CCL4 levels were reduced after dupilumab treatment. Serum CCL4 levels were positively correlated with FENO, serum IgE, and CCL17 levels. Thus, CCL4 released from epithelial cells via the innate immune system during type 2 airway inflammation may function as a useful biomarker for the condition.

Association between Gut Microbiota and Body Composition in Japanese General Population: A Focus on Gut Microbiota and Skeletal Muscle.

This study aimed to investigate the gut microbial genera associated with skeletal muscle mass, using a large-scale survey from the standpoint of preventing sarcopenia. A total of 848 participants were included in the analysis. The mean (SD) ages of men (n = 353) and women (n = 495) were 50.0 (12.9) years and 50.8 (12.8) years, respectively. Body composition was assessed using appendicular skeletal muscle mass/body weight (ASM/BW), ASM, and BW. Additionally, the relationship between gut microbial genera and body composition was analyzed. The means (SD) of ASM/BW were 34.9 (2.4) % in men and 29.4 (2.9) % in women. Blautia and Bifidobacterium were positively associated with ASM/BW only in men (Blautia: ß = 0.0003, Bifidobacterium: ß = 0.0001). However, Blautia was negatively associated with BW (ß = -0.0017). Eisenbergiella was positively associated with ASM/BW (ß = 0.0209) and negatively associated with BW (ß = -0.0769) only in women. Our results indicate that Blautia, Bifidobacterium and Eisenbergiella, which are positively associated with ASM/BW, might help increase skeletal muscle mass. ASM/BW may clarify the relationship between gut microbiota and skeletal muscle mass without being affected by obesity or excess body fat mass.

Clinicopathological investigation of secretory carcinoma cases including a successful treatment outcome using entrectinib for high-grade transformation: a case report.

BACKGROUND: Secretory carcinoma (SC) of the salivary gland is a recently described malignant tumor harboring characteristic ETV6-NTRK3 gene fusion. SC generally has a favorable clinical course, and is currently regarded as a low-grade carcinoma. However, a small subset of SCs demonstrates aggressive clinical features with histologically high-grade transformed morphology, the molecular pathogenesis of which has not yet been elucidated. In this study, we performed a clinicopathological and molecular genetic study of patients with SC of the head and neck displaying various clinical characteristics to investigate the differences of pathological and molecular genetics between low-grade and high-grade components of SC. CASE PRESENTATION: Three cases with SC of the head and neck, including a conventional low-grade SC and two high-grade transformed SCs are described. High-grade transformed SCs with histological features such as nuclear polymorphism, distinctive nucleoli and increased mitotic activity developed locoregional recurrence and distant metastasis. Immunohistochemical analysis revealed that low- and high-grade components showed different expression patterns for S-100 protein and mammaglobin, whereas all examined components were positive for p-STAT5. p53-positive cell population was markedly higher in one case with high-grade transformed SC. The proliferative activity of high-grade components was markedly increased, with the Ki-67 labeling index ranging up to 30-32%. A fluorescence in situ hybridization study with an ETV6 (12p13) break apart probe revealed split signals in the nuclei in all 3 cases. A targeted next-generation sequencing-based fusion assay demonstrated that all 6 clinical samples from the 3 patients showed the presence of the ETV6-NTRK3 fusion transcripts. One patient with high-grade transformed SC showed a dramatic clinical response to the pan-TRK inhibitor, entrectinib, for the treatment of locoregional recurrence and pulmonary metastasis. CONCLUSIONS: High-grade transformed SC showed aggressive clinical and pathological features with increased Ki-67 labeling index. Molecular genetic study of gene rearrangement appears to be beneficial treatment as the presence of ETV6-NTRK3 translocation may represent a therapeutic target in SC, particularly the high-grade transformed type.

Pathogenic changes in group 2 innate lymphoid cells (ILC2s) in a steroid-insensitive asthma model of mice.

A certain population of asthma patients is resistant to steroid therapy, whereas the mechanisms remain unclear. One of characteristic features of steroid-resistant asthma patients is severe airway eosinophilia based on type-2 inflammation. Aims of this study were: 1) to develop a murine model of steroid-resistant asthma, 2) to elucidate that predominant cellular source of a type-2 cytokine, IL-5 was group 2 innate lymphoid cells (ILC2s), 3) to analyze pathogenic alteration of ILC2s in the severe asthma, and 4) to evaluate therapeutic potential of anti-IL-5 monoclonal antibody (mAb) on the steroid-resistant asthma. Ovalbumin (OVA)-sensitized BALB/c mice were intratracheally challenged with OVA at 5 or 500 µg/animal 4 times. Development of airway eosinophilia and remodeling in 5-µg OVA model were significantly suppressed by 1 mg/kg dexamethasone, whereas those in 500-µg OVA model were relatively insensitive to the dose of dexamethasone. ILC2s isolated from the lung of the steroid-insensitive model (500-µg OVA) produced significantly larger amounts of IL-5 in response to IL-33/TSLP than ILC2s from the steroid-sensitive model (5-µg OVA). Interestingly, TSLP receptor expression on ILC2s was up-regulated in the steroid-insensitive model. Treatment with anti-IL-5 mAb in combination with dexamethasone significantly suppressed the airway remodeling of the steroid-insensitive model. In conclusion, multiple intratracheal administration of a high dose of antigen induced steroid-insensitive asthma in sensitized mice. IL-5 was mainly produced from ILC2s, phenotype of which had been pathogenically altered probably through the up-regulation of TSLP receptors. IL-5 blockage could be a useful therapeutic strategy for steroid-resistant asthma.

Low Level of Serum Cadmium in Relation to Blood Pressures Among Japanese General Population.

Hypertension (HT) is an important risk factor for mortality and morbidity. Previous studies showed that cadmium (Cd) was associated with increased blood pressures and the prevalence of HT. This study hypothesized that Cd, regardless of its level, may increase blood pressures/HT. The objective of this study was to examine the associations between a low level of serum Cd concentration and blood pressures/HT among a general population in the Iwaki area, Japan. This was a cross-sectional study, conducted in the Aomori prefecture with 1144 volunteers aged over 19 years old, who were participants of the Iwaki health check-up in 2014. The study assessed questionnaire survey, body composition, and serum Cd concentrations. Median serum Cd concentration was 0.06 ng/mL (interquartile range 0.05-0.08 ng/mL) among our study population. Compared to the lowest quintile of serum Cd concentration group, the highest quintile of serum Cd concentration group had 4.9 mmHg higher systolic blood pressure (SBP) (95% confidence interval [CI] 1.53-8.31, p < 0.01) and 2.4 mmHg higher diastolic blood pressure (DBP) (95% CI 0.36-4.34, p < 0.05), compared to the lowest quintile group. Similarly, the highest quintile of serum Cd concentration group had 1.7 times higher prevalence of HT (95% CI 1.10-2.51, p < 0.05) than the lowest quintile group. This study identified that higher serum Cd concentration was significantly, positively, associated with SBP and DBP and HT prevalence. This study provided evidence for the associations between environmental exposure to Cd and blood pressures/HT which should be considered for future preventive measures.

Prevalence of whiplash injury and its association with quality of life in local residents in Japan: A cross sectional study.

BACKGROUND: Associations between whiplash injuries and quality of life (QOL) have been previously published by conducting surveys among patients. This study aimed to investigate the prevalence of whiplash injuries in a Japanese community, and the association between whiplash injuries and QOL was also determined. METHODS: In all, 1140 volunteers participated in this study, filled out a questionnaire about whether they had experienced a whiplash injury, or had any neck pain or neck-shoulder stiffness in the previous 3 months, and completed the Medical Outcomes Study 36-Item Short-Form Health Survey. QOL was evaluated from the eight domain scores, and the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. We compared the characteristics, habits, history, medication, body mass index, and health-related QOL (eight domains, PCS and MCS scores) between the groups with whiplash injuries and no whiplash injuries for each sex. Multiple linear regressions with the forced-entry procedure were performed to evaluate the effects of a whiplash injury on the PCS and MCS. A p-value of <0.05 was considered statistically significant. RESULTS: The prevalence of whiplash injuries was 7.7% and 9.6% in men and women, respectively. The percentage of those who experienced whiplash injuries with symptoms persisting for more than 3 months was 34.3% and 24.2% in men and women, respectively. The prevalence of neck symptoms was significantly higher in the whiplash injury group than in the non-whiplash injury group. Multiple linear regression analysis showed that, although whiplash injuries were associated with poor health-related QOL in men, age was more associated with health-related QOL than whiplash injuries in both sexes. CONCLUSION: The prevalence of whiplash injuries was 7.7% and 9.6% in men and women in local residents in Japan, respectively. Whiplash injuries were poorly associated with a poor health-related QOL in men (P = 0.015).

Renadirsen, a Novel 2'OMeRNA/ENA® Chimera Antisense Oligonucleotide, Induces Robust Exon 45 Skipping for Dystrophin In Vivo.

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease caused by out-of-frame or nonsense mutation in the dystrophin gene. It begins with a loss of ambulation between 9 and 14 years of age, followed by various other symptoms including cardiac dysfunction. Exon skipping of patients' DMD pre-mRNA induced by antisense oligonucleotides (AOs) is expected to produce shorter but partly functional dystrophin proteins, such as those possessed by patients with the less severe Becker muscular dystrophy. We are working on developing modified nucleotides, such as 2'-O,4'-C-ethylene-bridged nucleic acids (ENAs), possessing high nuclease resistance and high affinity for complementary RNA strands. Here, we demonstrate the preclinical characteristics (exon-skipping activity in vivo, stability in blood, pharmacokinetics, and tissue distribution) of renadirsen, a novel AO modified with 2'-O-methyl RNA/ENA chimera phosphorothioate designed for dystrophin exon 45 skipping and currently under clinical trials. Notably, systemic delivery of renadirsen sodium promoted dystrophin exon skipping in cardiac muscle, skeletal muscle, and diaphragm, compared with AOs with the same sequence as renadirsen but conventionally modified by PMO and 2'OMePS. These findings suggest the promise of renadirsen sodium as a therapeutic agent that improves not only skeletal muscle symptoms but also other symptoms in DMD patients, such as cardiac dysfunction.

Omalizumab Restores Response to Corticosteroids in Patients with Eosinophilic Chronic Rhinosinusitis and Severe Asthma.

Eosinophilic chronic rhinosinusitis (ECRS), which is a subgroup of chronic rhinosinusitis with nasal polyps, is characterized by eosinophilic airway inflammation extending across both the upper and lower airways. Some severe cases are refractory even after endoscopic sinus surgery, likely because of local steroid insensitivity. Although real-life studies indicate that treatment with omalizumab for severe allergic asthma improves the outcome of coexistent ECRS, the underlying mechanisms of omalizumab in eosinophilic airway inflammation have not been fully elucidated. Twenty-five patients with ECRS and severe asthma who were refractory to conventional treatments and who received omalizumab were evaluated. Nineteen of twenty-five patients were responsive to omalizumab according to physician-assessed global evaluation of treatment effectiveness. In the responders, the levels of peripheral blood eosinophils and fractionated exhaled nitric oxide (a marker of eosinophilic inflammation) and of CCL4 and soluble CD69 (markers of eosinophil activation) were reduced concomitantly with the restoration of corticosteroid sensitivity. Omalizumab restored the eosinophil-peroxidase-mediated PP2A inactivation and steroid insensitivity in BEAS-2B. In addition, the local inflammation simulant model using BEAS-2B cells incubated with diluted serum from each patient confirmed omalizumab's effects on restoration of corticosteroid sensitivity via PP2A activation; thus, omalizumab could be a promising therapeutic option for refractory eosinophilic airway inflammation with corticosteroid resistance.

Treg and IL-1 receptor type 2-expressing CD4+ T cell-deleted CD4+ T cell fraction prevents the progression of age-related hearing loss in a mouse model.

We investigated the association between cellular immunity and age-related hearing loss (ARHL) development using three CD4+ T cell fractions, namely, naturally occurring regulatory T cells (Treg), interleukin 1 receptor type 2-expressing T cells (I1R2), and non-Treg non-I1R2 (nTnI) cells, which comprised Treg and I1R2-deleted CD4+ T cells. Inoculation of the nTnI fraction into a ARHL murine model, not only prevented the development of ARHL and the degeneration of spiral ganglion neurons, but also suppressed serum nitric oxide, a source of oxidative stress. Further investigations on CD4+ T cell fractions could provide novel insights into the prevention of aging, including presbycusis.