RESUMO
BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease. Although murine studies have demonstrated that type 2 innate lymphoid cells (ILCs) mediate type 2 skin inflammation, their role in skin fibrosis in AD remains unclear. This study investigated whether type 2 ILCs are involved in skin fibrosis using an AD-like murine model. METHODS: C57BL/6 mice were treated epicutaneously with Aspergillus fumigatus (Af) for 5 consecutive days per week for 5 weeks to induce skin fibrosis. Mature lymphocyte deficient Rag1-/- mice were also used to investigate the role of type 2 ILCs in skin fibrosis. RESULTS: The clinical score and transepidermal water loss (TEWL) were significantly higher in the AD group than in the control group. The AD group also showed significantly increased epidermal and dermal thicknesses and significantly higher numbers of eosinophils, neutrophils, mast cells, and lymphocytes in the lesional skin than the control group. The lesional skin of the AD group showed increased stain of collagen and significantly higher levels of collagen than the control group (10.4 ± 2.2 µg/mg vs. 1.6 ± 0.1 µg/mg, P < 0.05). The AD group showed significantly higher populations of type 2 ILCs in the lesional skin compared to the control group (0.08 ± 0.01% vs. 0.03 ± 0.01%, P < 0.05). These findings were also similar with the AD group of Rag1-/- mice compared to their control group. Depletion of type 2 ILCs with anti-CD90.2 monoclonal antibodies significantly improved clinical symptom score, TEWL, and infiltration of inflammatory cells, and significantly decreased levels of collagen were observed in the AD group of Rag1-/- mice (1.6 ± 0.0 µg/mg vs. 4.5 ± 0.3 µg/mg, P < 0.001). CONCLUSION: In the Af-induced AD-like murine model, type 2 ILCs were elevated, with increased levels of collagen. Additionally, removal of type 2 ILCs resulted in decreased collagen levels and improved AD-like pathological findings. These findings suggest that type 2 ILCs play a role in the mechanism of skin fibrosis in AD.
Assuntos
Dermatite Atópica , Modelos Animais de Doenças , Fibrose , Proteínas de Homeodomínio , Imunidade Inata , Linfócitos , Camundongos Endogâmicos C57BL , Pele , Animais , Dermatite Atópica/patologia , Dermatite Atópica/imunologia , Linfócitos/imunologia , Camundongos , Pele/patologia , Pele/imunologia , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Aspergillus fumigatus/imunologia , Colágeno/metabolismo , Camundongos Knockout , Mastócitos/imunologia , Eosinófilos/patologia , Eosinófilos/imunologia , FemininoRESUMO
BACKGROUND: Intensive care unit-acquired weakness (ICU-AW) is a syndrome characterized by a long-term muscle weakness often observed in sepsis-surviving patients during the chronic phase. Although ICU-AW is independently associated with increased mortality, effective therapies have yet to be established. Programmed death-1 (PD-1) inhibitors have attracted attention as potential treatments for reversing immune exhaustion in sepsis; however, its impact on ICU-AW remains to be elucidated. Here, we study how PD-1 deficiency affects sepsis-induced skeletal muscle dysfunction in a preclinical sepsis model. METHODS: Chronic sepsis model was developed by treating wild-type (WT) and PD-1 knockout (KO) mice with caecal slurry, followed by resuscitation with antibiotics and saline. Mice were euthanized on days 15-17. Body weights, muscle weights, and limb muscle strengths were measured. Interleukin 13 (IL-13) and PD-1 expressions were examined by flow cytometry. Messenger RNA (mRNA) expressions of slow-twitch muscles were measured by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). In an in vitro study, C2C12 myotubes were treated with lipopolysaccharide (LPS) and recombinant IL-13 followed by gene expression measurements. RESULTS: WT septic mice exhibited decreased muscle weight (quadriceps, P < 0.01; gastrocnemius, P < 0.05; and tibialis anterior, P < 0.01) and long-term muscle weakness (P < 0.0001), whereas PD-1 KO septic mice did not exhibit any reduction in muscle weights and strengths. Slow-twitch specific mRNAs, including myoglobin (Mb), troponin I type 1 (Tnni1), and myosin heavy chain 7 (Myh7) were decreased in WT skeletal muscle (Mb, P < 0.0001; Tnni1, P < 0.05; and Myh7, P < 0.05) after sepsis induction, but mRNA expressions of Tnni1 and Myh7 were increased in PD-1 KO septic mice (Mb, not significant; Tnni1, P < 0.0001; and Myh7, P < 0.05). Treatment of C2C12 myotube cells with LPS decreased the expression of slow-twitch mRNAs, which was restored by IL-13 (Mb, P < 0.0001; Tnni1, P < 0.001; and Myh7, P < 0.05). IL-13 production was significantly higher in ILC2s compared to T cells in skeletal muscle (P < 0.05). IL-13-producing ILC2s in skeletal muscle were examined and found to increase in PD-1 KO septic mice, compared with WT septic mice (P < 0.05). ILC2-derived IL-13 was increased by PD-1 KO septic mice and thought to protect the muscles from experimental ICU-AW. CONCLUSIONS: Long-term muscle weakness in experimental ICU-AW was ameliorated in PD-1 KO mice. ILC2-derived IL-13 production in skeletal muscles was increased in PD-1 KO mice, thereby suggesting that IL-13 alleviates muscle weakness during sepsis. This study demonstrates the effects of PD-1 blockade in preserving muscle strength during sepsis through an increase in ILC2-derived IL-13 and may be an attractive therapeutic target for sepsis-induced ICU-AW.
RESUMO
Hematopoietic stem cell (HSC)-independent lymphopoiesis has been elucidated in murine embryos. However, our understanding regarding human embryonic counterparts remains limited. Here, we demonstrated the presence of human yolk sac-derived lymphoid-biased progenitors (YSLPs) expressing CD34, IL7R, LTB, and IRF8 at Carnegie stage 10, much earlier than the first HSC emergence. The number and lymphopoietic potential of these progenitors were both significantly higher in the yolk sac than the embryo proper at this early stage. Importantly, single-cell/bulk culture and CITE-seq have elucidated the tendency of YSLP to differentiate into innate lymphoid cells and dendritic cells. Notably, lymphoid progenitors in fetal liver before and after HSC seeding displayed distinct transcriptional features, with the former closely resembling those of YSLPs. Overall, our data identified the origin, potential, and migratory dynamics of innate lymphoid-biased multipotent progenitors in human yolk sac before HSC emergence, providing insights for understanding the stepwise establishment of innate immune system in humans.
RESUMO
BACKGROUND: Acute liver failure (ALF) is a life-threatening disorder that progresses from self-limiting acute liver injury (ALI). Microcirculatory disturbance characterized by sinusoidal hypercoagulation and subsequent massive hypoxic hepatocyte damage have been proposed to be the mechanism by which ALI deteriorates to ALF; however, the precise molecular pathway of the sinusoidal hypercoagulation remains unknown. Here, we analyzed ALI patients and mice models to uncover the pathogenesis of ALI with microcirculatory disturbance. METHODS: We conducted a single-center retrospective study for ALI and blood samples and liver tissues were analyzed to evaluate the microcirculatory disturbance in ALI patients (n = 120). Single-cell RNA sequencing analysis (scRNA-seq) was applied to the liver from the concanavalin A (Con A)induced mouse model of ALI. Interferon-gamma (IFNγ) and tumor necrosis factor-alpha knockout mice, and primary human liver sinusoidal endothelial cells (LSECs) were used to assess the mechanism of microcirculatory disturbance. RESULTS: The serum IFNγ concentrations were significantly higher in ALI patients with microcirculatory disturbance than in patients without microcirculatory disturbance, and the IFNγ was upregulated in the Con A mouse model which presented microcirculatory disturbance. Hepatic IFNγ expression was increased as early as 1 hour after Con A treatment prior to sinusoidal hypercoagulation and hypoxic liver damage. scRNA-seq revealed that IFNγ was upregulated in innate lymphoid cells and stimulated hepatic vascular endothelial cells at the early stage of liver injury. In IFNγ knockout mice treated with Con A, the sinusoidal hypercoagulation and liver damage were remarkably attenuated, concomitant with the complete inhibition of CD40 and tissue factor (TF) upregulation in vascular endothelial cells. By ligand-receptor analysis, CD40-CD40 ligand interaction was identified in vascular endothelial cells. In human LSECs, IFNγ upregulated CD40 expression and TF was further induced by increased CD40-CD40 ligand interaction. Consistent with these findings, hepatic CD40 expression was significantly elevated in human ALI patients with microcirculatory disturbance. CONCLUSION: We identified the critical role of the IFNγ-CD40 axis as the molecular mechanism of microcirculatory disturbance in ALI. This finding may provide novel insights into the pathogenesis of ALI and potentially contribute to the emergence of new therapeutic strategies for ALI patients.
RESUMO
Innate lymphocytes (ILCs) rapidly respond to and protect against invading pathogens and cancer. ILCs include natural killer (NK) cells, ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer (LTi) cells and include type I, type II, and type III immune cells. While NK cells have been well recognized for their role in antiviral immunity, other ILC subtypes are emerging as players in antiviral defense. Each ILC subset has specialized functions that uniquely impact the antiviral immunity and health of the host depending on the tissue microenvironment. This review focuses on the specialized functions of each ILC subtype and their roles in antiviral immune responses across tissues. Several viruses within infection-prone tissues will be highlighted to provide an overview of the extent of the ILC immunity within tissues and emphasize common versus virus-specific responses.
Assuntos
Imunidade Inata , Linfócitos , Especificidade de Órgãos , Viroses , Humanos , Animais , Linfócitos/imunologia , Linfócitos/virologia , Viroses/imunologia , Especificidade de Órgãos/imunologia , Vírus/imunologiaRESUMO
Group 3 innate lymphoid cells (ILC3s) are tissue-resident immune lymphocytes that critically regulate intestinal homeostasis, organogenesis, and immunity. ILC3s possess the capacity to "sense" the inflammatory environment within tissues, especially in the context of pathogen challenges that imprints durable non-antigen-specific changes in ILC3 function. As such, ILC3s become a new actor in the emerging field of trained innate immunity. Here, we summarize recent discoveries regarding ILC3 responses to bacterial challenges and the role these encounters play in triggering trained innate immunity. We further discuss how signaling events throughout ILC3 ontogeny potentially control the development and function of trained ILC3s. Finally, we highlight the open questions surrounding ILC3 "training" the answers to which may reveal new insights into innate immunity. Understanding the fundamental concepts behind trained innate immunity could potentially lead to the development of new strategies for improving immunity-based modulation therapies for inflammation, infectious diseases, and cancer.
Assuntos
Imunidade Inata , Linfócitos , Transdução de Sinais , Humanos , Animais , Linfócitos/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Homeostase , Inflamação/imunologia , Microbioma Gastrointestinal/imunologia , Intestinos/imunologiaRESUMO
Recently, considerable attention has been directed toward innate-like T cells (ITCs) and innate lymphoid cells (ILCs) owing to their indispensable contributions to immune responses, tissue homeostasis, and inflammation. Innate-like T cells include NKT cells, MAIT cells, and γδ T cells, whereas ILCs include NK cells, type 1 ILCs (ILC1s), type 2 ILCs (ILC2s), and type 3 ILCs (ILC3s). Many of these ITCs and ILCs are distributed to specific tissues and remain tissue-resident, while others, such as NK cells and some γδ T cells, circulate through the bloodstream. Nevertheless, recent research has shed light on novel subsets of innate immune cells that exhibit characteristics intermediate between tissue-resident and circulating states under normal and pathological conditions. The local microenvironment frequently influences the development, distribution, and function of these innate immune cells. This review aims to consolidate the current knowledge on the functional heterogeneity of ITCs and ILCs, shaped by local environmental cues, with particular emphasis on IL-15, which governs the activities of the innate immune cells involved in type 1 immune responses.
Assuntos
Imunidade Inata , Linfócitos , Humanos , Células Matadoras Naturais , InflamaçãoRESUMO
Eosinophilic asthma is the most prevalent and well-defined phenotype of asthma. Despite a majority of patients responding to corticosteroid therapy and T2 biologics, there remains a subset that have recurrent asthma exacerbations, highlighting a need for additional therapies to fully ameliorate airway eosinophilia. Group 2 innate lymphoid cells (ILC2) are considered key players in the pathogenesis of eosinophilic asthma through the production of copious amounts of type 2 cytokines, namely IL-5 and IL-13. ILC2 numbers are increased in the airways of asthmatics and with the greatest numbers of activated ILC2 detected in sputa from severe prednisone-dependent asthma with uncontrolled eosinophilia. Although epithelial-derived cytokines are important mediators of ILC2 activation, emerging evidence suggests that additional pathways stimulate ILC2 function. The tumor necrosis factor super family (TNFSF) and its receptors (TNFRSF) promote ILC2 activity. In this review, we discuss evidence supporting a relationship between ILC2 and TNFSF/TNFRSF axis in eosinophilic asthma and the role of this relationship in severe asthma with airway autoimmune responses.
Assuntos
Asma , Eosinofilia Pulmonar , Humanos , Imunidade Inata , Linfócitos/metabolismo , Citocinas/metabolismoRESUMO
Triptolide (TP) is the major bioactive component of traditional Chinese medicine Tripterygium wilfordii Hook. F., a traditional Chinese medicinal plant categorized within the Tripterygium genus of the Celastraceae family. It is recognized for its therapeutic potential in addressing a multitude of diseases. Nonetheless, TP is known to exhibit multi-organ toxicity, notably hepatotoxicity, which poses a significant concern for the well-being of patients undergoing treatment. The precise mechanisms responsible for TP-induced hepatotoxicity remain unresolved. In our previous investigation, it was determined that TP induces heightened hepatic responsiveness to exogenous lipopolysaccharide (LPS). Additionally, natural killer (NK) cells were identified as a crucial effector responsible for mediating hepatocellular damage in this context. However, associated activating receptors and the underlying mechanisms governing NK cell represented innate lymphoid cell (ILC) activation remained subjects of inquiry and were not yet investigated. Herein, activating receptor Killer cell lectin like receptor K1 (NKG2D) of group 1 ILCs was specifically upregulated in TP- and LPS-induced acute liver failure (ALF), and in vivo blockade of NKG2D significantly reduced group 1 ILC mediated cytotoxicity and mitigated TP- and LPS-induced ALF. NKG2D ligand UL16-binding protein-like transcript 1 (MULT-1) was found upregulated in liver resident macrophages (LRMs) after TP administration, and LRMs did exhibit NK cell activating effect. Furthermore, M1 polarization of LRMs cells was observed, along with an elevation in intracellular tumor necrosis factor (TNF)-α levels. In vivo neutralization of TNF-α significantly alleviated TP- and LPS-induced ALF. In conclusion, the collaborative role of group 1 ILCs and LRMs in mediating hepatotoxicity was confirmed in TP- and LPS-induced ALF. TP-induced MULT-1 expression in LRMs was the crucial mechanism in the activation of group 1 ILCs via MULT-1-NKG2D signal upon LPS stimulation, emphasizing the importance of infection control after TP administration.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Diterpenos , Fenantrenos , Animais , Humanos , Camundongos , Subfamília K de Receptores Semelhantes a Lectina de Células NK , Lipopolissacarídeos/toxicidade , Imunidade Inata , Fenantrenos/toxicidade , Compostos de Epóxi/toxicidade , Células Matadoras Naturais , Macrófagos , Doença Hepática Induzida por Substâncias e Drogas/etiologiaRESUMO
Thawing of viably frozen human tissue T cells, ILCs, and NK cells and subsequent single-cell RNA sequencing reveals that recovery of cellular subclusters is variably impacted. While freeze-thawing does not alter the transcriptional profiles of cells, it upregulates genes and gene pathways associated with stress and activation.
Assuntos
Células Matadoras Naturais , Linfócitos T , Humanos , Congelamento , Análise de Sequência de RNARESUMO
Dendritic cell (DC) vaccines can stimulate the immune system to target cancer antigens, making them a promising therapy in immunotherapy. Clinical trials have shown limited effectiveness of DC vaccines, highlighting the need to enhance the immune responses they generate. Innate lymphoid cells (ILCs) are a diverse group of innate leukocytes that produce various cytokines and regulate the immune system. These cells have the potential to improve immunotherapies. There is not much research on how group 2 ILCs (ILC2s) communicate with DC vaccines. Therefore, examining the roles of DC vaccination in immune responses is crucial. Our research analyzed the effects of DC vaccination on the ILC2 populations and their cytokine production. By exploring the relationship between ILC2s and DCs, we aimed to understand how this could affect DC-based immunotherapies. The results showed an increase in the number of ILC2s in the local draining lymph node and spleen of tumor-free mice, as well as in the lungs of mice challenged with tumors in a pulmonary metastasis model. This suggests a complex interplay between DC-based vaccines and ILC2s, which is further influenced by the presence of tumors.
RESUMO
OBJECT: Recurrent tonsillitis and tonsillar hypertrophy are two common diseases in children for which tonsillectomy is the definitive solution. The underlying causes of both diseases are not fully known. The aim of this study was to identify the predominant innate lymphoid cells in both diseases of the palatine tonsils, which are known to play an important role in the immune system. METHODS: Children who underwent tonsillectomy were divided into two groups as recurrent tonsillitis and tonsillar hypertrophy according to the indication for surgery. The proportions of innate lymphoid cell (ILC) groups and IFN-gamma, IL-10 and IL-17 secreting T lymphocyte cells were determined in tonsil and blood samples obtained during surgery. Local and peripheral immune responses were evaluated. Innate immune responses and acquired immune responses were compared. RESULTS: The results of our study showed that the proportions of the innate lymphoid cell 1 group (ILC1) were similar in tonsil tissue in patients with recurrent tonsillitis and tonsil hypertrophy, with no statistically significant difference. It was observed that the innate lymphoid cell 2 group (ILC2) was the predominant group in tonsil hypertrophy, the innate lymphoid cell 3 group (ILC3) was the predominant innate lymphoid cell group in recurrent tonsillitis, and the proportion of IL-17 secreting T lymphocytes in blood and tonsillar mononuclear cells was higher in recurrent tonsillitis patients than in tonsil hypertrophy patients. CONCLUSION: With the results obtained, the predominant innate lymphoid cells in the pathogenesis of both diseases were identified and local and peripheral responses were compared. These findings may be a guide for possible medical treatments for both diseases in the future.
Assuntos
Tonsilectomia , Tonsilite , Criança , Humanos , Tonsila Palatina/cirurgia , Tonsila Palatina/patologia , Imunidade Inata , Interleucina-17 , Linfócitos/patologia , Tonsilite/cirurgia , Tonsilite/patologia , Hipertrofia/cirurgia , Doença Crônica , RecidivaRESUMO
Natural killer (NK) cells are innate immune cells critical for protective immune responses against infection and cancer. Although NK cells differentiate in the bone marrow (BM) in an interleukin-15 (IL-15)-dependent manner, the cellular source of IL-15 remains elusive. Using NK cell reporter mice, we show that NK cells are localized in the BM in scattered and clustered manners. NK cell clusters overlap with monocyte and dendritic cell accumulations, whereas scattered NK cells require CXCR4 signaling. Using cell-specific IL-15-deficient mice, we show that hematopoietic cells, but not stromal cells, support NK cell development in the BM through IL-15. In particular, IL-15 produced by monocytes and dendritic cells appears to contribute to NK cell development. These results demonstrate that hematopoietic cells are the IL-15 niche for NK cell development in the BM and that BM NK cells are present in scattered and clustered compartments by different mechanisms, suggesting their distinct functions in the immune response.
Assuntos
Medula Óssea , Interleucina-15 , Camundongos , Animais , Células da Medula Óssea , Diferenciação Celular , Células Matadoras NaturaisRESUMO
Background: Type 2 innate lymphoid cells (ILC2s) and NLRP3 inflammasome are related to allergic and inflammatory responses. NLRP3 inflammasome inhibitor MCC950 was demonstrated to ameliorate allergic rhinitis (AR) in animal models. Objective: To elucidate the effect of MCC950 on ILC2 responses in AR. Methods: NLRP3 inflammasome, ILC2s, IL-5+ILC2s, IL-13+ILC2s, and Th2-related factors were examined in 30 AR patients. ILC2s were identified as Lin-CRTH2+CD127+lymphocytes. ILC2s isolated from PBMCs were stimulated with LPS plus ATP. The effect of MCC950, IL-1ß, and IL-18 on ILC2 responses was detected by flow cytometry. AR models were established in 60 BALB/c mice. Nasal symptoms and ILC2 responses in the AR models after MCC950 treatment were detected. Human nasal epithelial cells were stimulated with IL-13 (10 ng/mL) and treated with MCC950 (10 µM). Results: AR patients showed activated NLRP3 inflammasome and increased ILC2 responses compared to controls. NLRP3 inflammasome levels in the AR patients were positively related to the proportion of ILC2s, IL-5+ILC2s, and IL-13+ILC2s in total PBMCs. MCC950 treatment or IL-1ß/IL-18 suppression inhibited ILC2 proliferation and Th2-related factors (GATA3, RORα, IL-5, and IL-13). MCC950 administration alleviated frequencies of nasal rubbing and sneezes in the AR models. ILC2s, IL-5+ILC2s, and IL-13+ILC2s in mice were reduced by MCC950. MCC950 inhibited NLRP3 inflammasome in the in vitro models of AR. Conclusion: MCC950 inhibited ILC2 responses in AR and mice models, suggesting that blocking NLRP3 inflammasome may be a promising target for AR clinical treatment.
Assuntos
Imunidade Inata , Rinite Alérgica , Humanos , Animais , Camundongos , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Interleucina-18 , Linfócitos/metabolismo , Interleucina-13 , Interleucina-5 , Rinite Alérgica/tratamento farmacológicoRESUMO
Group 2 innate lymphoid cells (ILC2s) are critical for the immune response against parasite infection and tissue homeostasis and involved in the pathogenesis of allergy and inflammatory diseases. Although multiple molecules positively regulating ILC2 development and activation have been extensively investigated, the factors limiting their population size and response remain poorly studied. Here, we found that CD45, a membrane-bound tyrosine phosphatase essential for T cell development, negatively regulated ILC2s in a cell-intrinsic manner. ILC2s in CD45-deficient mice exhibited enhanced proliferation and maturation in the bone marrow and hyperactivated phenotypes in the lung with high glycolytic capacity. Furthermore, CD45 signaling suppressed the type 2 inflammatory response by lung ILC2s and alleviated airway inflammation and pulmonary fibrosis. Finally, the interaction with galectin-9 influenced CD45 signaling in ILC2s. These results demonstrate that CD45 is a cell-intrinsic negative regulator of ILC2s and prevents lung inflammation and fibrosis via ILC2s.
Assuntos
Fibrose Pulmonar , Animais , Camundongos , Fibrose Pulmonar/prevenção & controle , Imunidade Inata , Linfócitos , Inflamação , Transdução de SinaisRESUMO
Asthma is characterized by airflow limitations resulting from bronchial closure, which can be either reversible or fixed due to changes in airway tissue composition and structure, also known as remodeling. Airway remodeling is defined as increased presence of mucins-producing epithelial cells, increased thickness of airway smooth muscle cells, angiogenesis, increased number and activation state of fibroblasts, and extracellular matrix (ECM) deposition. Airway inflammation is believed to be the main cause of the development of airway remodeling in asthma. In this chapter, we will review the development of the adaptive immune response and the impact of its mediators and cells on the elements defining airway remodeling in asthma.
Assuntos
Remodelação das Vias Aéreas , Asma , Humanos , Pulmão , Matriz Extracelular/fisiologia , Imunidade AdaptativaRESUMO
Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants characterized by alveolar growth arrest. Interleukin (IL)-33 and type 2 innate lymphoid cell (ILC2) affect type II alveolar epithelial cell (AECII) differentiation in BPD mice and may cause increased lung epithelial-mesenchymal transition (EMT). Amphiregulin (AREG) can be produced by ILC2 and is associated with tissue repair. However, the action mechanism of AREG produced by ILC2 to alveolar development in BPD is unclear. In this study, we aimed to demonstrate the role and mechanism of AREG in influencing AECII transdifferentiation in the lung tissue of BPD mice. The effects of ILC2-derived AREG on AECII transdifferentiation were verified in vivo and in vitro, and the role of IL-33 on ILC2-derived AREG in AECII transdifferentiation in BPD mice and a preliminary investigation of the role of AREG's receptor-epidermal growth factor receptor (EGFR) on AECII transdifferentiation. The results showed that neonatal mice developed severe lung injury after hyperoxia, and IL-33 induced AREG production via ILC2 affected normal AECII differentiation and promoted EMT. In addition, the blockade of EGFR was found to alleviate the impaired AECII differentiation under hyperoxia in an in vitro study. In summary, our study demonstrates that AREG secreted by ILC2 affects AECII transdifferentiation in BPD mice, which provides a new idea for the clinical treatment of BPD.
Assuntos
Displasia Broncopulmonar , Hiperóxia , Recém-Nascido , Animais , Camundongos , Humanos , Células Epiteliais Alveolares , Imunidade Inata , Interleucina-33 , Transdiferenciação Celular , Anfirregulina , Recém-Nascido Prematuro , Linfócitos , Modelos Animais de Doenças , Receptores ErbBRESUMO
Epigenetics plays a crucial role in gene regulation and cell function without changing the DNA sequence. The process of differentiation in eukaryotes during cellular morphogenesis is a paradigm of epigenetic change; stem cells develop into pluripotent cell lines in the embryo, eventually becoming terminally developed cells. Recently, epigenetic changes were shown to play an important role in immune cell development, activation and differentiation, which impacts chromatin remodeling, DNA methylation, post-translational histone modifications and small or lncRNA engagement. Innate lymphoid cells (ILCs) are newly identified immune cells that lack antigen receptors. ILCs differentiate from hematopoietic stem cells via multipotent progenitor stages. In this editorial, the authors discuss the epigenetic regulation of ILC differentiation and function.