Lymphocytes Research Articles

Neuronal-ILC2 interactions regulate pancreatic glucagon and glucose homeostasis

The immune system shapes body metabolism, while interactions between peripheral neurons and immune cells control tissue homeostasis and immunity. However, whether peripheral neuroimmune interactions orchestrate endocrine system functions remains unexplored. After fasting, mice lacking type 2 innate lymphoid cells (ILC2s) displayed disrupted glucose homeostasis, impaired pancreatic glucagon secretion, and inefficient hepatic gluconeogenesis. Additionally, intestinal ILC2s were found in the pancreas, which was dependent on their expression of the adrenergic beta 2 receptor. Targeted activation of catecholaminergic intestinal neurons promoted the accumulation of ILC2s in the pancreas. Our work provides evidence that immune cells can be regulated by neuronal signals in response to fasting, activating an inter-organ communication route that promotes pancreatic endocrine function and regulation of blood glucose levels.

The state of the rat liver during the toxic period of intoxication with polychlorinated biphenyls

BACKGROUND: Polychlorinated biphenyls have various toxic effects on the body of humans and animals, causing a violation of the liver barrier function. AIM: To study the dynamics of the relative liver mass and the morphology of liver tissue in experimental rats during the toxic period after subacute administration of polychlorinated biphenyls. MATERIAL AND METHODS: The model of intoxication with polychlorinated biphenyls was carried out on white male rats (n=60) weighing 200±15 g aged 3–4 months. The following experimental groups of animals were formed: experimental group “1st day” (n=10), experimental group “28th day” (n=10) and experimental group “56th day” (n=10). For each experimental group of rats, a comparison group “control group” (n=10) was created. The experimental groups (n=30) of animals were orally administered an oil suspension of polychlorinated biphenyls at a dose of 300 mg/kg of rat body weight for 28 days. Control rats received sunflower oil. For morphological examination, pieces of rat liver were taken on the 1st, 28th and 56th days of the experiment. The relative liver mass, percentage of normal, abnormal and degenerative forms of hepatocytes were calculated. Descriptive statistics with calculation of the median Me (Q1 25%, Q3 75%) were used for all data; the Mann–Whitney U-test was used for nonparametric samples. Differences were considered significant at p0.05. RESULTS: On the 1st day of the toxicogenic period, the relative liver weight of rats increased by 1.2 times (p=0.0496) compared to the control group. On the 28th day, the relative liver weight of the experimental group of rats statistically significantly decreased by 1.2 times (p=0.0152) compared to the control. By the end of the study (day 56), the relative liver weight statistically significantly increased by 1.5 times (p=0.0049) compared to the control value and by 1.8 times compared to day 28 (p=0.0036). Morphological analysis of the liver tissue of the experimental rats revealed abnormally enlarged hepatocytes (14%) on the 1st day after cessation of biphenyl administration. During the toxic period, the number of such cells increased: on the 28th day it was 35% (p=0.0002) and on the 56th day — 47% (p=0.0002), respectively. By the end of the experiment, necrotizing hepatocytes were determined (22%). In the liver, lymphoid cells were diffusely located along the intralobular sinusoidal capillaries; they were found in the interlobular loose connective tissue along the portal zone of the liver. CONCLUSION: In subacute intoxication of experimental animals with polychlorinated biphenyls, inflammatory and destructive histomorphological changes in the liver and an increase in its relative mass were revealed.

Acute and chronic systemic inflammation associated with canine nodular splenic lesions composed of heterogeneous cell components: four cases (2020‐2024)

ObjectivesTo describe the clinical presentation and clinicopathological findings of dogs with nodular splenic lesions composed of heterogeneous cell components associated with systemic inflammation and to provide information on the outcome after surgical resection.Materials and MethodsMedical records were searched for dogs with histologically and immunohistochemically characterised nodular splenic lesions with mixed stromal, histiocytic and lymphoid cells and the presence of systemic inflammatory markers at the time of diagnosis.ResultsFour dogs were included, of which three had an undifferentiated splenic stromal sarcoma and one had a splenic leiomyosarcoma. Fever and abdominal pain were reported in three and four cases, respectively. All dogs showed hyperglobulinaemia and marked changes in the serum protein electrophoresis profile. C‐reactive protein and fibrinogen concentrations were both increased in three cases. These abnormalities completely resolved after splenectomy. Moreover, two dogs had concomitant glomerular disease and one dog had liver amyloidosis. Three dogs were still alive and asymptomatic 1, 6 and 9 months after surgery. One dog died 16 months after the initial presentation due to complications related to progressive renal failure.Clinical SignificanceBased on this report, nodular splenic lesions with heterogeneous cell components may directly be associated with a pro‐inflammatory state and should be considered as part of the differential diagnosis of fever and hyperglobulinaemia in dogs. Furthermore, early recognition and treatment of these lesions could reduce the risk of systemic complications potentially associated with amyloid deposit and organ failure.

A population of c-kit + IL-17A + ILC2s in sputum from individuals with severe asthma supports ILC2 to ILC3 trans-differentiation

In prednisone-dependent severe asthma, uncontrolled sputum eosinophilia is associated with increased numbers of group 2 innate lymphoid cells (ILC2s). These cells represent a relatively steroid-insensitive source of interleukin-5 (IL-5) and IL-13 and are considered critical drivers of asthma pathology. The abundance of ILC subgroups in severe asthma with neutrophilic or mixed granulocytic (both eosinophilic and neutrophilic) airway inflammation, prone to recurrent infective exacerbations, remains unclear. Here, we found by flow cytometry that sputum ILC3s are increased in severe asthma with intense airway neutrophilia, whereas equivalently raised sputum ILC2s and ILC3s were found in severe asthma with mixed granulocytic inflammation. Unbiased clustering analyses identified an “intermediate-ILC2” population displaying markers of both ILC2s (prostaglandin D 2 receptor 2; CRTH2, IL-5, and IL-13) and ILC3s (c-kit and IL-17A) that were most abundant in severe asthma with mixed granulocytic airway inflammation. Intermediate ILC2s correlated with airway neutrophilia and were associated with increased amounts of IL-1β and IL-18 in sputum supernatants. Coculture of sort-purified canonical ILC2s with IL-1β and IL-18 in vitro up-regulated c-kit and IL-17A as well as gene expression profiles related to both type 2 and type 17 inflammatory pathways. Together, we have identified an intermediate-ILC2 phenotype in the airways of individuals with severe mixed granulocytic asthma, representing a candidate therapeutic target for controlling neutrophilic airway inflammation.

Multiple Myeloma Cells Shift the Fate of Cytolytic ILC2s Towards TIGIT-Mediated Cell Death

Background: Growing evidence attests to the multifaceted roles of group 2 innate lymphoid cells (ILC2s) in cancer immunity. They exhibit either pro- or anticancer activity depending on tumor type but their function in Multiple Myeloma (MM) is still not elucidated. Methods: The bone marrow (BM) and peripheral blood (PB) of patients (pts) with MM or precancerous conditions were collected, and specific properties of ILC2 subsets were assessed by flow cytometry. Results: By dissecting ILC2s according to c-Kit marker, we observed that NKp30 and NKG2D were mainly confined to c-Kithi ILC2s, while levels of DNAM-1 was significantly higher in fully mature c-Kitlo cells. Among the total MM-associated ILC2s (MM-ILC2s), we observed a significant increase in c-the Kitlo subset, but the expression of DNAM-1 in these cells was significantly reduced, especially in BM. Interestingly, MM-ILC2s from PB expressed granzyme B (GZMB), but its expression was impaired in BM-ILC2s. Accordingly, MM cells were susceptible to killing by MM-ILC2s derived from PB while eluding ILC2 surveillance in BM. Indeed, in MM-ILC2s derived from BM, the downregulation of DNAM-1 is accompanied by the upregulation of TIGIT, which mediate cell death in ILC2s upon recognition of the cognate ligands expressed by MM cells. These ILC2 changes appeared in clinical precursor conditions and eventually accumulated with disease progression. Conclusions: MM-ILC2s can act as cytolytic immune effectors that are fully competent in PB. However, MM cells shift ILC2 fate towards cell death in BM via the upregulation of TIGIT, thereby representing a potential therapeutic target to restore ILC2 antitumor activity.

Evaluating the Diagnostic Value of Lymphocyte Subsets in Bronchoalveolar Lavage Fluid and Peripheral Blood Across Various Diffuse Interstitial Lung Disease Subtypes

Diffuse interstitial lung diseases (ILD) include conditions with identifiable causes such as chronic eosinophilic pneumonia (CEP), sarcoidosis (SAR), chronic hypersensitivity pneumonitis (CHP), and connective tissue disease-associated interstitial pneumonia (CTD), as well as idiopathic interstitial pneumonia (IIP) of unknown origin. In non-IIP diffuse lung diseases, bronchoalveolar lavage (BAL) fluid appearance is diagnostic. This study examines lymphocyte subsets in BAL fluid and peripheral blood of 56 patients with diffuse ILD, excluding idiopathic pulmonary fibrosis (IPF), who underwent BAL for diagnostic purposes. Patients were classified into CEP, SAR, CHP, CTD, and IIP groups, and clinical data, BAL cell analysis, and peripheral blood mononuclear cell analysis were compared. Eosinophils and type 3 innate lymphocytes (ILC3s) were significantly increased in the BAL fluid of the CEP group. Receiver operating characteristic curve analysis identified eosinophils ≥ 8% in BAL cells and ILC3s ≥ 0.0176% in the BAL lymphocyte fraction as thresholds distinguishing CEP. SAR patients exhibited significantly elevated CD4/CD8 ratios in the BAL fluid, with a ratio of 3.95 or higher and type 1 innate lymphoid cell frequency ≥ 0.254% as differentiation markers. High Th1 cell frequency (≥17.4%) in BAL lymphocytes in IIP, elevated serum KL-6 (≥2081 U/mL) and SP-D (≥261 ng/mL) in CHP, and increased BAL neutrophils (≥2.0%) or a low CD4/CD8 ratio (≤1.2) in CTD serve as distinguishing markers for each ILD. Excluding CEP and SAR, CD4+ T cell frequencies, including Th1, Th17, and Treg cells in peripheral blood, may differentiate IIP, CHP, and CTD.

Maternal asthma imprints fetal lung ILC2s via glucocorticoid signaling leading to worsened allergic airway inflammation in murine adult offspring

The root of asthma can be linked to early life, with prenatal environments influencing risk. We investigate the effects of maternal asthma on the offspring’s lungs during fetal and adult life. Adult offspring of asthmatic mothers show an increase in lung group 2 innate lymphoid cell (ILC2) number and function with allergen-induced lung inflammation. Offspring of asthmatic mothers show phenotypic alteration of their lung ILC2s during fetal life, with increased expression of genes related to activation and glucocorticoid signaling. Furthermore, these offspring carry overlapping chromatin-accessible altered regions, including glucocorticoid receptor-binding regions in their lung ILC2s both at the fetal stage and adulthood, suggesting persistent prenatal epigenetic changes. Moreover, maternal exposure to glucocorticoids has similar effects on fetal lung ILC2s and contributes to allergen-induced lung inflammation during adulthood. Thus, asthma during pregnancy may have long-term effects on lung ILC2s in the offspring from the embryonic period, contributing to an increased risk of developing asthma.

Microbiota-derived proteins synergize with IL-23 to drive IL22 production in model type 3 innate lymphoid cells.

Microbiota-induced production of IL-22 by type 3 innate lymphoid cells (ILC3) plays an important role in maintaining intestinal health. Such IL-22 production is driven, in part, by IL-23 produced by gut myeloid cells that have sensed select microbial-derived mediators. The extent to which ILC3 can directly respond to microbial metabolites via IL-22 production is less clear, in part due to the difficulty of isolating and maintaining sufficient numbers of viable ILC3 ex vivo. Hence, we, herein, examined the response of the ILC3 cell line, MNK-3, to microbial metabolites in vitro. We observed that fecal supernatants (FS), by themselves, elicited modest levels of IL-22 and synergized with IL-23 to drive robust IL-22 production assayed by qRT-PCR and ELISA. The IL-22 synergistic activity of FS was not mimicked by an array of candidate microbial metabolites but could be attributed to bacterial proteins. Examining how MNK3 cells exposed to IL-23, FS, both, or neither via RNA-seq and immunoblotting indicated that FS activated MNK-3 cells in a distinct pattern from IL-23: FS activates p-38 MAPK while IL-23 activates STAT3 signaling pathways. Collectively, these studies indicate ILC3 sensing of microbiota proteins promotes IL-22 production suggesting the possibility of manipulating microbiota to increase IL-22 without risk of IL-23-mediated chronic inflammatory diseases.

AIP56, an AB toxin secreted by Photobacterium damselae subsp. piscicida, has tropism for myeloid cells

IntroductionThe AB-type toxin AIP56 is a key virulence factor of Photobacterium damselae subsp. piscicida (Phdp), inducing apoptosis in fish immune cells. The discovery of AIP56-like and AIP56-related toxins in diverse organisms, including human-associated Vibrio strains, highlights the evolutionary conservation of this toxin family, suggesting that AIP56 and its homologs may share conserved receptors across species. These toxins have potential for biotechnological applications, such as therapeutic protein delivery and immune modulation.MethodsHerein, the cell specificity of AIP56 for immune cells was characterized. The tropism of AIP56 for cells of the sea bass, mouse and human immune system was analyzed by following toxin internalization by flow cytometry and arrival of the toxin in the cytosol by evaluating the cleavage of NF-kB p65 by western blotting.ResultsOnly a small population of sea bass neutrophils internalized AIP56, indicating that most of the neutrophilic destruction during Phdp infection and/or AIP56 intoxication does not result from the direct action of the toxin. Moreover, the cellular tropism of AIP56 for myeloid cells was observed in the three species, including its preference for macrophages. Further, mouse and human M0 and M2-like macrophages internalized more toxin than M1-like macrophages. Despite the limited interaction of lymphoid cells with AIP56, mouse B1-cells were able to internalize the toxin, possibly due to its myeloid features.ConclusionAIP56 has tropism for sea bass, mouse and human myeloid cells, with greater affinity for macrophages. This points to an evolutionary conservation of its receptor(s) and mechanism of action across species, raising the possibility that AIP56-like and -related toxins may also play a role in pathogenesis. These findings are relevant for both pathogenicity and biomedical contexts.

Clinical characteristics of immunocompromised patients infected with COVID-19

Objective: To analyze the clinical features of COVID-19 infection in hospitalized immunocompromised patients in comparison with immunocompetent patients. Methods: A single-center retrospective observational study was conducted on 213 inpatients diagnosed with COVID-19 in the Peking University People's Hospital between December 2022 and October 2023. They were divided into an immunocompromised group (102 patients, 47.9%) and an immunocompetent group(111 patients, 52.1%), and clinical data were compared between the two groups. The immunocompromised group was further divided into death group (18 cases, 17.6%) and non-death group (84 cases, 82.4%). The differences in laboratory examination findings were compared. Further analysis was performed on the lymphocyte subset differences between the death group(10 patients, 9.8%) and the non-death group (36 patients, 35.3%) with complete data. Results: The proportion of severe and critical cases and the mortality rate, were significantly higher in the immunocompromised group than the immunocompetent group (47.1% vs. 40.5%, 18.6% vs. 9.0%, 17.6% vs. 9.0%,P<0.05). The immunocompromised group had lower vaccination rate (26.5% vs. 44.1%, P<0.05). Hypertension, kidney disease and infections were more common in the immunocompromised group (63.7% vs. 48.6%, 30.4% vs. 9.0%, 49.0% vs. 19.8%, all P<0.05). CT findings of consolidation (40.2% vs. 18.9%), rate of antiviral treatment (48.0% vs. 30.6%) and the positive duration of viral nucleic acid [median 14(7.0, 19.3) days vs. 9(7.0, 18.0) days] were higher in the immunocomprised group (all P<0.05). Lactate dehydrogenase (LDH), procalcitonin (PCT), interleukin-6 (IL-6) and ferritin were higher in the immunocompromised group than those in the immunocompetent group (all P<0.05). In the death group, neutrophils (NEU), C-reactive protein (CRP), PCT, IL-6, ferritin and D-dimer were higher, while lymphocytes (LY), CD4+T-cells, CD8+T-cells, B-cell counts and hemoglobin (HGB) were significantly lower than those in the non-death group (all P<0.05). Conclusions: More than 60% of patients in the immunocompromised group were classified as severe or critical type, with a higher mortality rate and decreased ability to clear severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Decreases in total lymphocytes, CD4+T lymphocytes, CD8+T lymphocytes, and B lymphocytes, along with elevated levels of procalcitonin, ferritin, and D-dimer, indicated poor prognosis.

Adaptive immune cells antagonize ILC2 homeostasis via SLAMF3 and SLAMF5.

Type 2 innate lymphoid cells (ILC2s) mainly reside in tissues with few lymphoid cells. How their tissue residency is regulated remains poorly understood. This study explores the inhibitory role of SLAM-family receptors (SFRs) on adaptive immune cells in ILC2 maintenance. We observed an increase in the population of ILC2s in Rag1-deficient mice. Homotypic engagement of SFRs between ILC2s and adaptive immune cells was identified as a potential mechanism. SFR deficiency led to an increase in ILC2s. Conditional deletion of SFRs on T and/or B cells led to an increased ILC2 abundance. Mechanistically, as ILC precursors differentiate into ILC2s, SFRs, primarily SLAMF3 and SLAMF5, are inhibitory, which impair IL-7-induced PI3K activation and enhance apoptosis via SHP-1. These findings reveal a mechanism by which adaptive immune cells negatively regulate the homeostasis of ILC2s and contribute to our understanding of the complex interplay between innate and adaptive immune cells in the regulation of immune responses.

Proposal for Clinical Management of Nodules Diagnosed as Atypia of Undetermined Significance via Thyroid Fine-Needle Aspiration Cytology in the Absence of Molecular Testing.

Molecular testing is recommended for risk stratification of atypia of undetermined significance (AUS) nodules in the USA; however, it is not routinely performed in some countries owing to limited availability and affordability. Here, we propose a risk stratification algorithm for AUS nodules when molecular testing is unavailable. We examined 304 (4.3%) AUS nodules among 7073 thyroid fine-needle aspiration cytology specimens examined at Kuma Hospital from January 2020 to December 2020. Clinical data were obtained from the medical records of Kuma Hospital. AUS with nuclear atypia and AUS-other each accounted for half of the total AUS nodules. The repeat aspiration rate was 19.7%; 61.7% of the nodules were reclassified as benign or malignant upon repeat aspiration. Resection rate and overall risk of malignancy (ROM) were 32.6% and 12.8%, respectively. Architectural atypia showed the lowest (1.1%) overall ROM in the AUS nodules. For AUS with nuclear atypia, nodules ≤ 10 mm in size showed significantly lower overall ROM than those of > 10 mm, and nodules with ultrasonographically low suspicion showed significantly lower overall ROM than those with intermediate to high suspicion. AUS nodules with atypical lymphoid cells, possible medullary thyroid carcinoma, or possible parathyroid lesion were confirmed using flow cytometry, biochemical testing using needle washout fluid or immunocytochemistry, respectively. Our proposed clinical management algorithm for each subdivision according to cytological findings, based on repeat aspiration rates, ROM, ultrasound findings and results of ancillary tests except for molecular testing, should be useful for the clinical management of AUS nodules.

Role of Arg1+ ILC2s and ILCregs in gestational diabetes progression

Innate lymphoid cells (ILCs) are a newly discovered subset of immune cells that are responsible for regulation of the immune microenvironment. In particular, the ILC categories ILC2s and regulatory ILCs (ILCregs) are associated with immunosuppression and chronic inflammation. Chronic low-grade inflammation leads to insulin resistance, a major etiological factor in gestational diabetes mellitus (GDM). However, the influence of ILCs on GDM remains poorly understood. Therefore, this study aims to investigate the potential role of ILCs in the development and progression of GDM. This study included 19 patients diagnosed with GDM and 19 age- and body mass index-matched individuals in the control group. Flow cytometry was employed to assess the frequency and function of ILC subsets in peripheral blood (PB), cord blood (CB), and placental tissues. Additionally, ELISA was utilized to measure the levels of the cytokines TNF-α, IFN-γ, TGF-β, and IL-4/10/13/22 in the serum samples of patients. Compared to the control group with normal pregnancy, significantly elevated levels of ILC2s, Arg1+ILC2s, and ILCregs were detected in the PB, CB, and placental tissues of the GDM group. With regard to inflammation-related cytokines, the levels of IL-13/22 in PB serum were significantly elevated, while the TGF-β levels were significantly reduced in the GDM group compared to the control group (CG). Further, in the CB serum samples, IL-13 levels were elevated in the GDM group. Additionally, a negative correlation was observed between the number of ILC3s and the number of ILCregs present in umbilical cord blood, while the IL-13 level in peripheral blood was negatively correlated with the number of ILC3s. The present findings indicate that chronic low-grade inflammation mediated by Arg-1+ILC2s and ILCregs is closely associated with the pathogenesis of GDM.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive. To dissect these, we performed genotype-phenotype correlations of 92 affected individuals harboring a pathogenic or likely pathogenic BCL11B variant, followed by immune phenotyping, analysis of chromatin immunoprecipitation DNA-sequencing data, dual-luciferase reporter assays, and molecular modeling. These integrative analyses enabled us to define three clinical subtypes of BCL11B-related disorders. It is likely that gene-disruptive BCL11B variants and missense variants affecting zinc-binding cysteine and histidine residues cause mild to moderate neurodevelopmental delay with increased propensity for behavioral and dental anomalies, allergies and asthma, and reduced type 2 innate lymphoid cells. Missense variants within C2H2-ZnF DNA-contacting α helices cause highly variable clinical presentations ranging from multisystem anomalies with demise in the first years of life to late-onset, hyperkinetic movement disorder with poor fine motor skills. Those not in direct DNA contact cause a milder phenotype through reduced, target-specific transcriptional activity. However, missense variants affecting C2H2-ZnFs, DNA binding, and "specificity residues" impair BCL11B transcriptional activity in a target-specific, dominant-negative manner along with aberrant regulation of alternative DNA targets, resulting in more severe and unpredictable clinical outcomes. Taken together, we suggest that the phenotypic severity and variability is largely dependent on the DNA-binding affinity and specificity of altered BCL11B proteins.

Model-based analysis for investigating the impact of tumor size, lymphocyte and neutrophil on the survival of breast cancer 4 T1 tumor-bearing mice

Survival is one of the foremost endpoints in cancer therapy, and parametric survival analysis could comprehensively demonstrate the overall result of various different baseline and longitudinal factors. In this study, the survival of triple negative breast cancer 4 T1 tumor-bearing mice treated by gemcitabine (GEM) and dexamethasone (DEX) was investigated with model-based analysis. The tumor size, lymphocyte (LY) and neutrophil (NE) of 4 T1 tumor-bearing BALB/c mice were collected, and the PK/PD models of these longitudinal data were established in a sequential manner, respectively. The parametric time-to-event (TTE) model of survival was developed and the PK/PD models were tested and integrated as time-varying prognostic factors. The final model was evaluated and externally validated. LY and NE influence the survival directly, while tumor size showed its indirect impact on survival by affecting LY. The exposure of GEM significantly improved the survival results but DEX did not bring extra benefit. The models established in this study quantitatively characterized the abnormal increasing of LY and NE due to tumor progression in 4 T1 tumor-bearing mice and also demonstrate their relationship with survival outcomes, and further provide a modeling framework to demonstrate potential prognostic factors of survival and evaluate the efficacy of different therapies.

Early changes in intestinal lymphoid and myeloid populations in experimental autoimmune encephalomyelitis.

Intestinal immunity is associated with several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes. Recent evidence also suggests its implication in the pathogenesis of autoimmune diseases affecting the central nervous system, such as multiple sclerosis (MS). However, there is ongoing debate regarding which part of the intestinal tract contributes to the development of MS. Therefore, our study aimed to explore the early changes in lymphoid and myeloid immune cells populations in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We also sought to determine the roles of the colon and/or small intestine in the pathogenesis of EAE. By using flow cytometry, we revealed a transient increase in T and B lymphocytes in the ileal lamina propria of EAE mice just before the onset of motor symptoms. Additionally, we highlighted an increase in dendritic cells and monocytes/macrophages in the colonic lamina propria of EAE animals during the presymptomatic phase. Altogether, our findings indicate that both small intestine and colon are involved in the pathogenesis of EAE, despite engaging distinct immunological processes. This study provides new insights for understanding the roles of intestinal lymphoid and myeloid immune cells on the pathogenesis of MS and other autoimmune diseases.

Single‐Cell RNA Sequencing Analysis Reveals Exercise‐Induced Transcriptional Dynamics in Half‐Marathon Runners

ABSTRACTPrevious studies in sports science suggested that regular exercise has a positive impact on human health. However, the effects of endurance sports and their underlying mechanisms are still not completely understood. One of the main debates regards the modulation of immune dynamics in high‐intensity exercise. As part of the “Run 4 Science” project in Verona, Italy, we conducted a single‐cell RNA sequencing analysis on half‐marathon amateur runners to investigate the transcriptional dynamics of peripheral blood mononuclear cells following endurance exercise. Blood samples were collected from four participants before and after running a half‐marathon to carry out a comprehensive transcriptomic analysis of immune cells at the single‐cell level. Our analysis revealed significant alterations in the transcriptional profiles following endurance physical exercise. Modulations in myeloid cells suggested the activation of stress response (6 related pathways, p &lt; 0.04) and pathways related to viral processes (4 related pathways, p &lt; 0.03), while in lymphoid cells they hinted to a shift towards immune activation (24 related pathways, p &lt; 0.01). Additionally, transcriptional changes in platelets point to an activation of the coagulation process (5 related pathways, p &lt; 0.005). Single‐cell data was also analyzed following a pseudo‐bulk approach (i.e., simulating a bulk RNAseq experiment) to gain further biological insights. Our findings suggest that a pseudo‐bulk analysis could offer complementary findings to classical single‐cell analysis methods and demonstrate that endurance physical exercise, such as running a half‐marathon, induces substantial changes in the transcriptional dynamics of immune cells. These insights contribute to a better understanding of the immune modulation mediated by endurance exercise and may inform future training routines or nutritional guidelines based on individual gene expression levels.

Leucemia felina: revisão

ABSTRACT: Among the hematopoietic neoplasms, leukemias are caused by myeloid or lymphoid cells in the bone marrow, which can either be acute with an unfavorable prognosis and mostly affect cats that tested positive for feline viral leukemia (FeLV) or chronic in older cats that have a poor prognosis. Leukemias have several classifications in which the differentiation depends on complementary tests, such as blood profile, myelogram, cytology. and flow cytometry, which help determine the best treatment for the animal.

The intestinal fungus Aspergillus tubingensis promotes polycystic ovary syndrome through a secondary metabolite.

Polycystic ovary syndrome (PCOS) affects 6%-10% of women of reproductive age and is known to be associated with disruptions in the gut bacteria. However, the role of the gut mycobiota in PCOS pathology remains unclear. Using culture-dependent and internal transcribed spacer 2 (ITS2)-sequencing methods, we discovered an enrichment of the gut-colonizable fungus Aspergillus tubingensis in 226 individuals, with or without PCOS, from 3 different geographical areas within China. Colonization of mice with A.tubingensis led to a PCOS-like phenotype due to inhibition of Aryl hydrocarbon receptor (AhR) signaling and reduced interleukin (IL)-22 secretion in intestinal group 3 innate lymphoid cells (ILC3s). By developing a strain-diversity-based-activity metabolite screening workflow, we identified secondary metabolite AT-C1 as an endogenous AhR antagonist and a key mediator of PCOS. Our findings demonstrate that an intestinal fungus and its secondary metabolite play a critical role in PCOS pathogenesis, offering a therapeutic strategy for improving the management of the disease.

Innate Lymphoid Cells in COVID-19: Bystanders or Active Contributors?

Innate Lymphoid Cells in COVID-19: Bystanders or Active Contributors?