SARS-CoV-2 spike-specific nasal-resident CD49a+CD8+ memory T cells exert immediate effector functions with enhanced IFN-γ production.

Virus-specific nasal resident T cells are important for protection against subsequent infection with a similar virus. Here we examine the phenotypes and functions of SARS-CoV-2-specific T cells in the nasal mucosa of vaccinated individuals with breakthrough infection (BTI) or without infection. Nasal tissues are obtained from participants during sinus surgery. Analysis of activation-induced markers implicates that a considerable proportion of spike (S)-reactive nasal CD8+ T cells express CD103, a tissue-resident marker. MHC-I multimer staining is performed to analyze the ex vivo phenotype and function of SARS-CoV-2 S-specific CD8+ T cells. We detect multimer+CD8+ T cells with tissue-resident phenotypes in nasal tissue samples from vaccinees without infection as well as vaccinees with BTI. Multimer+CD8+ T cells remain present in nasal tissues over one year after the last exposure to S antigen, although the frequency decreases. Upon direct ex vivo stimulation with epitope peptides, nasal multimer+CD8+ T cells-particularly the CD49a+ subset-exhibit immediate effector functions, including IFN-γ production. CITE-seq analysis of S-reactive AIM+CD8+ T cells confirms the enhanced effector function of the CD49a+ subset. These findings indicate that among individuals previously exposed to S antigen by vaccination or BTI, S-specific nasal-resident CD49a+CD8+ memory T cells can rapidly respond to SARS-CoV-2 during infection or reinfection.

Differential regulation of viral entry-associated genes modulated by inflammatory cytokines in the nasal epithelium.

This study aimed to investigate the impact of different types of nasal inflammation on the regulation of entry-associated genes of respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus 229E (HCoV-229E), and influenza virus, in the nasal epithelium. Subjects were classified into three groups: control, eosinophilic chronic rhinosinusitis (ECRS), and noneosinophilic CRS (NECRS) groups. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2), alanyl aminopeptidase (ANPEP), dipeptidyl peptidase 4 (DPP4), and beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1), and beta-galactoside alpha-2,3-sialyltransferase 4 (ST3GAL4) were selected as key entry-associated genes for SARS-CoV-2, HCoV-229E, MERS-CoV, and influenza, respectively, and were evaluated. Brushing samples obtained from each group and human nasal epithelial cells cultured using an air-liquid interface system were treated for 7 days with typical inflammatory cytokines and analyzed using real-time polymerase chain reaction. Western blot analysis and confocal microscopy were performed. The entry-associated genes showed distinct regulation patterns in response to each interleukin-4 (IL-4), interleukin-13 (IL-13), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Specifically, ACE2 significantly decreased in type 2 cytokines (IL-4 and IL-13), while TMPRSS2 significantly decreased in type 1 cytokines (TNF-α and IFN-γ). ANPEP significantly decreased in both types of cytokines. Remarkably, DPP4 significantly increased in type 2 cytokines and decreased in type 1 cytokines. Moreover, ST6GAL1 and ST3GAL4 significantly increased in type 2 cytokines and decreased in type 1 cytokines, particularly IFN-γ. These findings were supported by western blot analysis and confocal imaging results, especially for ACE2 and DPP4. The findings regarding differential regulation suggest that patients with ECRS, primarily mediated by type 2 inflammation, may have lower susceptibility to SARS-CoV-2 and HCoV-229E infections but higher susceptibility to MERS-CoV and influenza infections.

Outcomes and Predictors of Success Following Multilevel Surgery in Positional and Nonpositional Obstructive Sleep Apnea.

OBJECTIVE: To assess the surgical outcomes and identify predictors of surgical success in patients with positional and non-positional obstructive sleep apnea following multilevel airway surgery. STUDY DESIGN: Retrospective cohort study. SETTING: Singe-tertiary medical center. METHODS: This study included 158 patients with obstructive sleep apnea who underwent multilevel airway surgery. Patients were divided into 2 groups according to position dependency: "positional patients" group (n = 100), and "nonpositional patients" group (n = 58). The characteristics and surgical outcomes of the 2 groups were compared. RESULTS: The nonpositional group included younger and more obese patients in comparison to the positional group. Moreover, the nonpositional group had more severe disease than the positional group. Both groups showed overall improvement after surgery, and the surgical success rate did not differ significantly between the 2 groups (nonpositional, 41.4% vs positional, 48.0%; P = .424). Notably, 69.0% of patients belonging to the non-positional group converted to positional group postoperatively. Logistic regression analysis revealed that larger tonsil size, female sex, and higher mean O2 saturation were associated with higher success rate in the positional group, whereas larger tonsil size was associated with surgical success in the nonpositional group. CONCLUSION: Both nonpositional and positional groups showed improvements following multilevel airway surgery, and surgery induced a transition from nonpositional to positional group. Given that the factors related to surgical success differed between the two groups, surgeons should consider position dependency and these distinct factors during decision-making.

Sinonasal seromucinous hamartoma: a single institution case series combined with a narrative review of the literature.

PURPOSE: This study aimed to investigate the clinical and histopathological characteristics of sinonasal seromucinous hamartomas (SHs). METHODS: Eight patients with sinonasal SH and treated at a tertiary hospital between November 2005 and September 2023 were included. Additionally, a systematic review of published articles was conducted, analyzing 48 cases of SH described in the literature. RESULTS: Among the eight patients treated at our institution, tumors originated from the posterior nasal cavity in four patients and middle turbinate and middle meatus were the primary origin in two patients each. Coexistence of inflammatory nasal polyps (NPs) was observed in four cases. Histopathologically, four patients exhibited focal respiratory epithelial adenomatoid hamartoma (REAH) features, and low-grade dysplasia was found in one patient. A combined analysis with previous literature revealed that 46.3% of all cases originated in the anterior nasal cavity. The proportions of cases accompanied by NPs and those with focal REAH features were 20.5% and 39.1%, respectively. Additionally, the frequencies of cases exhibiting dysplastic features (5.4%) and recurrence (2.1%) were low. Remarkably, tumors originating from the anterior region tended to have a higher frequency of dysplasia than those originating from the posterior region, although this difference was not statistically significant (p = 0.0996). CONCLUSION: Patients with sinonasal SH showed favorable treatment outcomes following surgical resection. Focal REAH features and accompanying NPs were frequently observed. A substantial proportion of cases originate in the anterior nasal cavity, and these tumors may exhibit a high tendency for dysplasia.

Airway epithelial CD47 plays a critical role in inducing influenza virus-mediated bacterial super-infection.

Respiratory viral infection increases host susceptibility to secondary bacterial infections, yet the precise dynamics within airway epithelia remain elusive. Here, we elucidate the pivotal role of CD47 in the airway epithelium during bacterial super-infection. We demonstrated that upon influenza virus infection, CD47 expression was upregulated and localized on the apical surface of ciliated cells within primary human nasal or bronchial epithelial cells. This induced CD47 exposure provided attachment sites for Staphylococcus aureus, thereby compromising the epithelial barrier integrity. Through bacterial adhesion assays and in vitro pull-down assays, we identified fibronectin-binding proteins (FnBP) of S. aureus as a key component that binds to CD47. Furthermore, we found that ciliated cell-specific CD47 deficiency or neutralizing antibody-mediated CD47 inactivation enhanced in vivo survival rates. These findings suggest that interfering with the interaction between airway epithelial CD47 and pathogenic bacterial FnBP holds promise for alleviating the adverse effects of super-infection.

Mucosal Immunity against SARS-CoV-2 in the Respiratory Tract.

The respiratory tract, the first-line defense, is constantly exposed to inhaled allergens, pollutants, and pathogens such as respiratory viruses. Emerging evidence has demonstrated that the coordination of innate and adaptive immune responses in the respiratory tract plays a crucial role in the protection against invading respiratory pathogens. Therefore, a better understanding of mucosal immunity in the airways is critical for the development of novel therapeutics and next-generation vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses. Since the coronavirus disease 2019 pandemic, our knowledge of mucosal immune responses in the airways has expanded. In this review, we describe the latest knowledge regarding the key components of the mucosal immune system in the respiratory tract. In addition, we summarize the host immune responses in the upper and lower airways following SARS-CoV-2 infection and vaccination, and discuss the impact of allergic airway inflammation on mucosal immune responses against SARS-CoV-2.

Impact of Non-Pharmaceutical Interventions on the Incidence and Treatment of Chronic Rhinosinusitis during the COVID-19 Pandemic: A Nationwide Retrospective Cohort Study.

Many countries have implemented non-pharmaceutical interventions (NPIs) to prevent the spread of COVID-19. However, the impacts of NPIs on the epidemiology and treatment of chronic rhinosinusitis (CRS) remain unclear. We analyzed 671,216 patients to investigate changes in the incidence rate and treatment frequency of CRS using Korean nationwide health insurance data between 2017 and 2021. The incidence rate (p < 0.001) and the number of outpatients (p < 0.001), patients hospitalized (p < 0.001), and patients prescribed antibiotics (p < 0.001) or steroids (p = 0.024) were significantly lower in the pandemic period than in the pre-pandemic period; however, the number of patients who underwent surgery was not different (p = 0.205). Additionally, the frequency of surgeries per patient was significantly lower in patients during the pandemic period (p < 0.001). In the interrupted time series analysis, the trends in the number of outpatients (p < 0.001), patients hospitalized (p < 0.001), patients who underwent surgery (p < 0.001), and patients prescribed antibiotics (p < 0.001) or steroids (p < 0.001) significantly changed after the onset of the COVID-19 pandemic. In summary, NPI implementation during the COVID-19 pandemic was associated with a reduction in the incidence and treatment of CRS.

Visualization of the relationship between electrogustometry and whole mouth test using multidimensional scaling.

Interpreting the relationship between different taste function tests of different stimuli, such as chemical and electrical stimulation, is still poorly understood. This study aims to analyze visually as well as quantitatively how to interpret the relationship of results between taste function tests using different stimuli. Patients who underwent the whole mouth test and Electrogustometry (EGM) at a tertiary medical center between August 2018 and December 2018 were reviewed retrospectively with electronic medical records. Of the 110 patients, a total of 86 adults who self-reported that their taste function was normal through a questionnaire were enrolled. EGM measured the thresholds of the chorda tympani (CT) and glossopharyngeal nerve (GL) area of the tongue. The whole mouth test measured detection and recognition thresholds for sweet, salty, bitter, sour, and umami taste. Statistical analyses of Pearson's, Spearman's rank and polyserial correlation and multidimensional scaling (MDS) was performed. The EGM threshold for the average value of both CT regions and the recognition threshold of the whole mouth test were significantly correlated in sweet, salty, bitter, and sour taste (r = 0.244-0.398, P < 0.05), and the detection threshold was correlated only significant in sweet (r = 0.360, P = 0.007). In the MDS analysis results, the three-dimensional (D) solution was chosen over the 2-D solution because of the lower stress. Detection-, recognition threshold of whole mouth test and EGM thresholds of CT and GL area, those were standardized by Z-score, formed well-distinguished sections in the MDS analyses. The EGM threshold of the CT area was closer to the detection and recognition thresholds than the EGM threshold of the GL area. In general, the EGM threshold was closer to the recognition threshold than the detection threshold for each taste. Overall, visualization of the relationship of whole mouth test and EGM by MDS was in good agreement with quantitative analysis. EGM and whole mouth test seem to reflect different aspects of taste. However, when interpreting the EGM results, the EGM threshold of the CT area will show more similarity to the recognition threshold than the detection threshold for the whole mouth test.

Spatiotemporal dynamics of the development of mouse olfactory system from prenatal to postnatal period.

Introduction: The olfactory epithelium (OE) and olfactory bulb (OB) are the major components of the olfactory system and play critical roles in olfactory perception. However, the embryonic development of OE and OB by using the olfactory specific genes has not been comprehensively investigated yet. Most previous studies were limited to a specific embryonic stage, and very little is known, till date, about the development of OE. Methods: The current study aimed to explore the development of mouse olfactory system by spatiotemporal analysis of the histological features by using the olfactory specific genes of olfactory system from the prenatal to postnatal period. Results: We found that OE is divided into endo-turbinate, ecto-turbinate, and vomeronasal organs, and that putative OB with putative main and accessory OB is formed in the early developmental stage. The OE and OB became multilayered in the later developmental stages, accompanied by the differentiation of olfactory neurons. Remarkably, we found the development of layers of olfactory cilia and differentiation of OE to progress dramatically after birth, suggesting that the exposure to air may facilitate the final development of OE. Discussion: Overall, the present study laid the groundwork for a better understanding of the spatial and temporal developmental events of the olfactory system.

KIR+CD8+ and NKG2A+CD8+ T cells are distinct innate-like populations in humans.

Subsets of the human CD8+ T cell population express inhibitory NK cell receptors, such as killer immunoglobulin-like receptors (KIRs) and NKG2A. In the present study, we examine the phenotypic and functional characteristics of KIR+CD8+ T cells and NKG2A+CD8+ T cells. KIRs and NKG2A tend to be expressed by human CD8+ T cells in a mutually exclusive manner. In addition, TCR clonotypes of KIR+CD8+ T cells barely overlap with those of NKG2A+CD8+ T cells, and KIR+CD8+ T cells are more terminally differentiated and replicative senescent than NKG2A+CD8+ T cells. Among cytokine receptors, IL12Rß1, IL12Rß2, and IL18Rß are highly expressed by NKG2A+CD8+ T cells, whereas IL2Rß is expressed by KIR+CD8+ T cells. IL-12/IL-18-induced production of IFN-γ is prominent in NKG2A+CD8+ T cells, whereas IL-15-induced NK-like cytotoxicity is prominent in KIR+CD8+ T cells. These findings suggest that KIR+CD8+ and NKG2A+CD8+ T cells are distinct innate-like populations with different cytokine responsiveness.

Calprotectin in chronic rhinosinusitis eosinophil extracellular traps.

BACKGROUND: Calprotectin is an antimicrobial peptide primarily secreted by neutrophils. Furthermore, calprotectin secretion increases in patients with chronic rhinosinusitis (CRS) with polyps (CRSwNP) and positively correlates with neutrophil markers. However, CRSwNP is known to be associated with type 2 inflammation related to tissue eosinophilia. Therefore, the authors investigated calprotectin expression in eosinophils and eosinophil extracellular traps (EETs) and explored the associations between tissue calprotectin and the clinical findings of patients with CRS. METHODS: A total of 63 patients participated, and patients diagnosed with CRS were classified based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score. The authors performed hematoxylin and eosin staining, immunohistochemistry, immunofluorescence with calprotectin, myeloperoxidase (MPO), major basic protein (MBP), and citrullinated histone H3 with the participant's tissues. Finally, correlations between calprotectin and the clinical data were examined. RESULTS: Calprotectin-positive cells are co-localized not only in MPO-positive cells but also in MBP-positive cells in human tissues. Calprotectin was also involved in EETs and neutrophil extracellular traps. The number of calprotectin-positive cells in the tissue was positively correlated with the number of tissue and blood eosinophils. In addition, calprotectin in the tissue is associated with the olfactory function, Lund-Mackay computed tomography score, and JESREC score. CONCLUSIONS: Calprotectin, known to be secreted by neutrophils, in CRS was also expressed in eosinophils. In addition, calprotectin, which functions as an antimicrobial peptide, may play an important role in the innate immune response based on its EET involvement. Therefore, calprotectin expression could reflect as a disease severity biomarker for CRS.

Clinical Characteristics and Surgical Outcomes of Obstructive Sleep Apnea Patients With Mixed Apnea Components.

OBJECTIVE: This study was aimed to investigate clinical implications of mixed apnea (MA) in patients with obstructive sleep apnea (OSA), particularly whether surgical outcomes differ between OSA patients with and without MA events. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary medical center. METHODS: Eighty-eight patients with OSA who underwent multilevel upper airway surgery were included. Patients were divided into 2 groups according to the presence of MA events: "pure group" (n = 30) and "mixed group" (n = 58). The clinical characteristics and surgical outcomes were compared between the 2 groups. RESULTS: The mixed group included more males (P = .020) and hypertensive patients (P = .009) and had a higher apnea-hypopnea index (AHI; P < .001) than the pure group. The surgical success rate was lower in the mixed group (29.3%) than in the pure group (73.3%; P < .001). Furthermore, the postoperative improvements in total AHI (P < .001), supine AHI (P < .001), and oxygen desaturation index (P = .006) were lower in the mixed group than in the pure group. Logistic regression analysis confirmed that the presence of MA (P = .002) was an independent predictor of poor surgical outcomes in patients with OSA. CONCLUSION: OSA patients with MA showed different clinical features and poor surgical outcomes compared to those without MA. These results imply that OSA with MA components may have a distinct pathophysiology, and the presence of MA should be considered in the surgical treatment of OSA.

Comparison of clinical features and surgical outcomes between hypopnea- and apnea-predominant obstructive sleep apnea.

OBJECTIVES: This study is aimed to investigate the differences in the clinical features and surgical outcomes between hypopnea- and apnea-predominant obstructive sleep apnea (OSA). DESIGN: Cohort study. SETTING: Single tertiary care centre. PARTICIPANTS: This study included 190 patients with OSA who underwent multilevel upper airway surgery between September 2012 and September 2021. The patients were divided into two groups according to the proportion of each respiratory event: hypopnea-predominant (n = 102) and apnea-predominant (n = 88). MAIN OUTCOME MEASURES: The primary outcome measure was the percentage improvement in the apnea-hypopnea index (AHI) from baseline AHI after surgery. RESULTS: The apnea-predominant group included more male patients and had higher AHI, respiratory disturbance index (RDI) and oxygen desaturation index (ODI) than the hypopnea-predominant group. Both groups showed significant improvements in AHI, apnea index, RDI, supine AHI, REM AHI, non-REM AHI, ODI, lowest O2 saturation and Epworth Sleepiness Scale scores following the surgery. Notably, hypopnea index increased after surgery in the apnea-predominant OSA group. Although the improvement in the absolute value of AHI by surgery was significantly greater in the apnea-predominant group than in the hypopnea-predominant group, the two groups showed no significant difference in the percentage improvement in AHI from baseline AHI. CONCLUSION: Patients with apnea-predominant OSA had more severe disease than those with hypopnea-predominant OSA; however, surgical outcomes, as evaluated by percentage AHI improvement, were comparable between the two groups. In addition, multilevel upper airway surgery may induce the transition from apnea to hypopnea in patients with apnea-predominant OSA.

Identification of a distinct NK-like hepatic T-cell population activated by NKG2C in a TCR-independent manner.

BACKGROUND & AIMS: The liver provides a unique niche of lymphocytes enriched with a large proportion of innate-like T cells. However, the heterogeneity and functional characteristics of the hepatic T-cell population remain to be fully elucidated. METHODS: We obtained liver sinusoidal mononuclear cells from the liver perfusate of healthy donors and recipients with HBV-associated chronic liver disease (CLD) during liver transplantation. We performed a CITE-seq analysis of liver sinusoidal CD45+ cells in combination with T cell receptor (TCR)-seq and flow cytometry to examine the phenotypes and functions of liver sinusoidal CD8+ T cells. RESULTS: We identified a distinct CD56hiCD161-CD8+ T-cell population characterized by natural killer (NK)-related gene expression and a uniquely restricted TCR repertoire. The frequency of these cells among the liver sinusoidal CD8+ T-cell population was significantly increased in patients with HBV-associated CLD. Although CD56hiCD161-CD8+ T cells exhibit weak responsiveness to TCR stimulation, CD56hiCD161-CD8+ T cells highly expressed various NK receptors, including CD94, killer immunoglobulin-like receptors, and NKG2C, and exerted NKG2C-mediated NK-like effector functions even in the absence of TCR stimulation. In addition, CD56hiCD161-CD8+ T cells highly respond to innate cytokines, such as IL-12/18 and IL-15, in the absence of TCR stimulation. We validated the results from liver sinusoidal CD8+ T cells using intrahepatic CD8+ T cells obtained from liver tissues. CONCLUSIONS: In summary, the current study found a distinct CD56hiCD161-CD8+ T-cell population characterized by NK-like activation via TCR-independent NKG2C ligation. Further studies are required to elucidate the roles of liver sinusoidal CD56hiCD161-CD8+ T cells in immune responses to microbial pathogens or liver immunopathology. LAY SUMMARY: The role of different immune cell populations in the liver is becoming an area of increasing interest. Herein, we identified a distinct T-cell population that had features similar to those of natural killer (NK) cells - a type of innate immune cell. This distinct population was expanded in the livers of patients with chronic liver disease and could thus have pathogenic relevance.

Is obstructive sleep apnea associated with erythrocytosis? A systematic review and meta-analysis.

Objective: The aim of this systematic review and meta-analysis was to investigate the association between obstructive sleep apnea (OSA) and erythrocytosis. Methods: The PubMed, Web of Science, and Cochrane Library databases were searched for articles examining hematocrit values in patients with OSA and control individuals published till September 1, 2021. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated, and subgroup analyses were performed. Results: Eleven eligible studies with a total of 4608 patients with OSA were included in this meta-analysis. Pooled outcomes revealed that hematocrit values were significantly higher in patients with OSA than in controls (SMD, 0.19; 95% CI, 0.08-0.29; p < .01). When studies were stratified by disease severity, the significant differences in hematocrit values between patients and controls were only observed in the severe OSA group (SMD, 0.34; 95% CI, 0.08-0.59; p < .01), but not in the mild and moderate OSA groups. In subgroup analyses according to sex and publication year, significant differences in hematocrit values between patients and controls remained stable in studies with only female patients (SMD, 0.25; 95% CI, 0.12-0.38; p < .01) and in studies published after 2012 (SMD, 0.17; 95% CI, 0.06-0.28, p < .01). Conclusion: Our meta-analysis revealed that the hematocrit value was significantly increased in patients with OSA, particularly in severe patients, compared with that in controls. However, the elevation was modest, and the hematocrit value is expected to be within the normal range in patients with OSA. These data suggest that OSA leads to slight increases in hematocrit but does not cause clinically significant erythrocytosis.

Impaired antibacterial response of liver sinusoidal Vγ9+Vδ2+ T cells in patients with chronic liver disease.

OBJECTIVE: The liver acts as a frontline barrier against diverse gut-derived pathogens, and the sinusoid is the primary site of liver immune surveillance. However, little is known about liver sinusoidal immune cells in the context of chronic liver disease (CLD). Here, we investigated the antibacterial capacity of liver sinusoidal γδ T cells in patients with various CLDs. DESIGN: We analysed the frequency, phenotype and functions of human liver sinusoidal γδ T cells from healthy donors and recipients with CLD, including HBV-related CLD (liver cirrhosis (LC) and/or hepatocellular carcinoma (HCC)), alcoholic LC and LC or HCC of other aetiologies, by flow cytometry and RNA-sequencing using liver perfusates obtained during living donor liver transplantation. We also measured the plasma levels of D-lactate and bacterial endotoxin to evaluate bacterial translocation. RESULTS: The frequency of liver sinusoidal Vγ9+Vδ2+ T cells was reduced in patients with CLD. Immunophenotypic and transcriptomic analyses revealed that liver sinusoidal Vγ9+Vδ2+ T cells from patients with CLD were persistently activated and pro-apoptotic. In addition, liver sinusoidal Vγ9+Vδ2+ T cells from patients with CLD showed significantly decreased interferon (IFN)-γ production following stimulation with bacterial metabolites and Escherichia coli. The antibacterial IFN-γ response of liver sinusoidal Vγ9+Vδ2+ T cells significantly correlated with liver function, and inversely correlated with the plasma level of D-lactate in patients with CLD. Repetitive in vitro stimulation with E. coli induced activation, apoptosis and functional impairment of liver sinusoidal Vγ9+Vδ2+ T cells. CONCLUSION: Liver sinusoidal Vγ9+Vδ2+ T cells are functionally impaired in patients with CLD. Bacterial translocation and decreasing liver functions are associated with functional impairment of liver sinusoidal Vγ9+Vδ2+ T cells.

IL-17A-producing sinonasal MAIT cells in patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: Diverse immune cells contribute to the pathogenesis of chronic rhinosinusitis (CRS), an inflammatory disease of the nasal cavity and paranasal sinuses. However, whether mucosal-associated invariant T (MAIT) cells are present in human sinonasal tissues remains unclear. Furthermore, the characteristics of sinonasal MAIT cells have not been studied in patients with CRS. OBJECTIVE: We investigated the phenotype, function, and clinical implications of MAIT cells in patients with CRS. METHODS: Peripheral blood and sinonasal tissue were obtained from patients with CRS with (CRSwNP) or without nasal polyps (CRSsNP) and healthy controls. MAIT cells were analyzed by flow cytometry. RESULTS: We found that MAIT cells are present in human sinonasal tissues from healthy controls and patients with CRS. The sinonasal MAIT cell population, but not peripheral blood MAIT cells, from patients with CRSsNP, noneosinophilic CRSwNP (NE-NP), or eosinophilic CRSwNP (E-NP) had a significantly higher frequency of activated cells marked by CD38 expression. In functional analysis, the sinonasal MAIT cell population from NE-NP and E-NP had a significantly higher frequency of IL-17A+ cells but lower frequency of IFN-γ+ or TNF+ cells than control sinonasal tissues. Furthermore, CD38 expression and IL-17A production by sinonasal MAIT cells significantly correlated with disease extent evaluated by the Lund-Mackay computed tomography score in patients with E-NP. CONCLUSIONS: Sinonasal MAIT cells exhibit an activated phenotype and produce higher levels of IL-17A in patients with CRSwNP. These alterations are associated with the extent of disease in patients with E-NP.