Role Of Innate Lymphoid Cells Research Articles

T-bet+ILC3 in peripheral blood is increased in the ankylosing spondylitis with high disease activity.

Ankylosing spondylitis (AS) is a chronic autoimmune disease characterized by systemic inflammation, often resulting in fusion of the spine and peripheral joints. This study aimed to investigate the role of innate lymphoid cells (ILCs) in AS patients with high disease activity. Blood samples were collected from healthy controls and AS patients categorized by high or low disease activity. Systemic inflammation was quantified through C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR), alongside disease activity scores such as Ankylosing Spondylitis Disease Activity Score(ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index(BASDAI). The levels of different ILC subsets and the expression of T-box transcription factor 21 (T-bet) and retinoic-acid-receptor-related orphan receptor gamma (RORγt) in peripheral blood were analyzed via flow cytometry. Additionally, 24 cytokines in plasma were measured using a Luminex liquid suspension chip. The proportion of total ILCs and the distribution of ILC subsets in peripheral blood varied with AS disease activity scores. Specifically, the frequencies of total ILCs and ILC3s were significantly elevated in AS patients with high disease activity (AS-HA). The frequency and absolute number of ILC3s showed a positively correlation with disease severity scores. Furthermore, T-bet+ILC3s were significantly increased in the AS-HA group. Plasma levels of IL-17A and IFN-γ were positively correlated with the frequency of circulating-ILC3 in AS patients. These findings highlight the critical role of T-bet+ILC3s in the inflammatory process of AS, suggesting their potential as a therapeutic target for managing AS disease.

Role of Innate Lymphoid Cells on Laboratory Mice Routine Handling Process and their Effect on the Other Immunological Parameters

Introduction: Lab mice typically belong to the Mus musculus species. They are the prevailing choice for mammalian research and are utilized for studies in genetics, physiology, psychology, medicine, and various scientific fields. Aim of the study: The current research aimed to examine how frequently handling laboratory mice impacts their innate immune response through innate lymphoid cells, mucus secretion, as well as various physiological and biochemical blood parameters, and its potential implications on research outcomes. Study design: Sixty female mice were used in this study all animals were hosted under the same condition and treated with the same rotational animal handling process in different periods including animal control oral gavage and intraperitoneal, sub courteous, and intramuscular injection. Blood samples were gathered at four different time points to analyze various hematological and biochemical parameters, including (RBC, Hb, PCV, WBC, ALT, AST enzymes, and urea levels, etc.) while colon tissue were collected and the immunohistochemistry and PAS staining were preformed to evaluate the innate lymphoid cells and mucin secretion at three level through the experimental period. The results: Based on the findings, there were no notable variations in the levels of Hb and RBC. However, there was a noticeable increase in the WBC count for all animals after 4 minutes of handling, and the levels began to normalize after 10 and 30 minutes. As for the blood's biochemical parameters, including ALT, AST, creatinine, and urea, no details were provided. The results showed that there were no noteworthy alterations in these parameters throughout the entire experimental period. Conclusion: The handling of the animals is one of the most important factors that can influence the experimental results in lab mice. The WBCs and samples should be collected at least 30 minutes after the handling procedure.

Exploring the role of innate lymphoid cells in the periodontium: insights into immunological dynamics during orthodontic tooth movement.

The periodontal ligament (PDL) experiences considerable mechanical stresses between teeth and bone, vital for tissue adaptation, especially in orthodontic tooth movement (OTM). While recent research emphasizes the role of innate lymphoid cells (ILCs) in regulating sterile inflammation, their involvement in periodontal tissues during OTM remains largely unexplored. In this study, PDL tissues from orthodontic patients (n = 8) were examined using flow cytometry to detect ILC subtypes. Transwell co-culture systems were used to expose PDL cells to mechanical strain, followed by measuring migration and ratios of sorted ILC subtypes. Statistical analyses were conducted using paired Student's t-test, Kruskal-Wallis test, Dunn's post-test and one-way/two-way ANOVA with Tukey's post-test (p≤ 0.05; **, p≤ 0.01; ***, p≤ 0.001). Our findings demonstrate a significant increase in CD127+ CD161+ ILC frequencies in PDL tissues during OTM, indicating ILC involvement in sterile inflammation induced by orthodontic forces. Co-culture assays show directed migration of ILC subsets towards PDL cells and substantial proliferation and expansion of ILCs. This study is the first to comprehensively investigate the role of ILCs in sterile inflammation during OTM, revealing their presence and distribution within PDL tissues' innate immune response in vivo, and exploring their migratory and proliferative behavior in vitro. The results suggest a crosstalk between ILCs and PDL cells, potentially influencing the inflammatory response and tissue remodeling processes associated with OTM.

Role of innate lymphoid cells in oral squamous cell carcinoma microenvironment

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy. It has a high incidence, strong invasion ability, easy metastasis, poor curative effect, and poor prognosis. Innate lymphoid cells (ILCs) are an important part of immune cells located in the mucosal barrier, which play an important role in the occurrence, development and outcome of tumors. ILCs are the key cells for decoding the regulatory mechanism of tumor microenvironment and the signatures for tumor progression. This paper reviewed the latest progress on ILCs, summarized the possible characteristics and functions of ILCs in the microenvironment of OSCC, and explored the relationship between ILCs and the occurrence, development and immunotherapy of OSCC.

Abstract 2694: The role of innate lymphoid cells and innate like T cells in hepatocellular carcinoma

Abstract The major focus of cancer immunotherapy has been on conventional T cells due to their unique recognition of specific peptide antigens. Despite advances in the cancer immunotherapy field, including the use of atezolizumab and bevacizumab as first-line therapy for unresectable hepatocellular carcinoma (HCC), the overall mortality rate of HCC continues to rise. Innate lymphoid cells (ILC) and innate-like T cells (ILTC) are broadly categorized within the innate lymphoid population as playing an important role in inflammation, tissue repair and immune tolerance. Their ability to react rapidly to stimulants in their local tissue environment as well as to recruit and activate a variety of other immune cells makes these cells attractive targets for anti-tumor therapy. However, previous studies looking at ILCs and ILTCs in cancer have revealed both pro- and anti-tumor functions. Furthermore, the complex interplay between these cell populations in the tumor microenvironment is not well understood, particularly over the natural course of tumor development. In this study, we aim to better elucidate the role of ILC and ILTC populations in HCC progression in terms of both their kinetics and role as potential therapeutic targets. We performed hydrodynamic tail vein injections in mice with two different plasmid combinations to alter expression of commonly mutated oncogenes and tumor suppressors in human HCC (MYC;TP53 and MYC;CTNNB1). Histologic analysis of the livers was performed to determine appropriate time points to assess ILC and ILTC populations. We then designed a comprehensive 29-plex spectral flow panel to assess broad kinetic changes in the frequency of ILC, ILTC, and conventional T cell populations. We show that in early time points (4-7 days post-injection) when neoplastic transformation of hepatocytes has already occurred, mucosal-associated invariant T (MAIT) cells, group 1 ILCs, ILC2s, and ILC3s expand in frequency for both tumor models. Cytokine analysis shows a generalized decreased trend across timepoints in effector cytokine production in MAITs and group 1 ILCs, suggesting gradual dysfunction over time. Taken together, these preliminary findings show that ILC and ILTC populations expand early during tumor progression but gradually decrease in functionality with tumor progression. Citation Format: Patrick Huang, Benjamin Ruf, Rajiv Trehan, Dana Soika, Chi Ma, Tim F. Greten, Firouzeh Korangy. The role of innate lymphoid cells and innate like T cells in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2694.

Bridging Chronic Inflammation and Digestive Cancer: The Critical Role of Innate Lymphoid Cells in Tumor Microenvironments.

The incidence and mortality of digestive system-related cancers have always been high and attributed to the heterogeneity and complexity of the immune microenvironment of the digestive system. Furthermore, several studies have shown that chronic inflammation in the digestive system is responsible for cancer incidence; therefore, controlling inflammation is a potential strategy to stop the development of cancer. Innate Lymphoid Cells (ILC) represent a heterogeneous group of lymphocytes that exist in contrast to T cells. They function by interacting with cytokines and immune cells in an antigen-independent manner. In the digestive system cancer, from the inflammatory phase to the development, migration, and metastasis of tumors, ILC have been found to interact with the immune microenvironment and either control or promote these processes. The conventional treatments for digestive tumors have limited efficacy, therefore, ILC-associated immunotherapies are promising strategies. This study reviews the characterization of different ILC subpopulations, how they interact with and influence the immune microenvironment as well as chronic inflammation, and their promotional or inhibitory role in four common digestive system tumors, including pancreatic, colorectal, gastric, and hepatocellular cancers. In particular, the review emphasizes the role of ILC in associating chronic inflammation with cancer and the potential for enhanced immunotherapy with cytokine therapy and adoptive immune cell therapy.

Single cell multi-omic analysis identifies key genes differentially expressed in innate lymphoid cells from COVID-19 patients.

Innate lymphoid cells (ILCs) are enriched at mucosal surfaces where they respond rapidly to environmental stimuli and contribute to both tissue inflammation and healing. To gain insight into the role of ILCs in the pathology and recovery from COVID-19 infection, we employed a multi-omics approach consisting of Abseq and targeted mRNA sequencing to respectively probe the surface marker expression, transcriptional profile and heterogeneity of ILCs in peripheral blood of patients with COVID-19 compared with healthy controls. We found that the frequency of ILC1 and ILC2 cells was significantly increased in COVID-19 patients. Moreover, all ILC subsets displayed a significantly higher frequency of CD69-expressing cells, indicating a heightened state of activation. ILC2s from COVID-19 patients had the highest number of significantly differentially expressed (DE) genes. The most notable genes DE in COVID-19 vs healthy participants included a) genes associated with responses to virus infections and b) genes that support ILC self-proliferation, activation and homeostasis. In addition, differential gene regulatory network analysis revealed ILC-specific regulons and their interactions driving the differential gene expression in each ILC. Overall, this study provides mechanistic insights into the characteristics of ILC subsets activated during COVID-19 infection.

Commentary: On the Emerging Role of Innate Lymphoid Cells in Bladder Cancer.

Commentary: On the Emerging Role of Innate Lymphoid Cells in Bladder Cancer.

AB012. The potential role of innate lymphoid cells in thymic epithelial tumors

AB012. The potential role of innate lymphoid cells in thymic epithelial tumors

The Emerging Role of Innate Lymphoid Cells (ILCs) and Alarmins in Celiac Disease: An Update on Pathophysiological Insights, Potential Use as Disease Biomarkers, and Therapeutic Implications.

Celiac disease (CD) is an intestinal disease that develops in genetically predisposed individuals and is triggered by the ingestion of gluten. CD was considered a Th1-disease. Today, the role of Th17, IL-21, and IL-17A lymphocytes is well known. Inflammation is regulated by the activity of gluten-specific CD4+ T lymphocytes that produce pro-inflammatory cytokines, including IFN-γ, TNF-α, and IL-21, perpetuating the Th1 response. These cytokines determine an inflammatory state of the small intestine, with consequent epithelial infiltration of lymphocytes and an alteration of the architecture of the duodenal mucosa. B cells produce antibodies against tissue transglutaminase and against deamidated gliadin. Although the role of the adaptive immune response is currently known, the evidence about the role of innate immunity cells is still poorly understood. Epithelial damage determines the release of damage-associated molecular patterns (DAMPs), also known as alarmins. Together with the intestinal epithelial cells and the type 1 innate lymphoid cells (ILC1s), alarmins like TSLP, IL-33, and HMGB1 could have a fundamental role in the genesis and maintenance of inflammation. Our study aims to evaluate the evidence in the literature about the role of ILCs and alarmins in celiac disease, evaluating the possible future diagnostic and therapeutic implications.

Innate Lymphoid Cells and Interferons Limit Neurologic and Articular Complications of Brucellosis

Brucellosis is a globally significant zoonotic disease. Human patients with brucellosis develop recurrent fever and focal complications, including arthritis and neurobrucellosis. The current study investigated the role of innate lymphoid cells (ILCs) in the pathogenesis of focal brucellosis caused by Brucella melitensis. After footpad infection, natural killer cells and ILC1 cells both limited joint colonization by Brucella. Mice lacking natural killer cells, and in particular mice lacking all ILCs, also developed marked arthritis after footpad infection. Following pulmonary infection, mice lacking adaptive immune cells and ILCs developed arthritis, neurologic complications, and meningitis. Adaptive immune cells and ILCs both limited colonization of the brain by Brucella following pulmonary infection. Transcriptional analysis of Brucella-infected brains revealed marked up-regulation of genes associated with inflammation and interferon responses, as well as down-regulation of genes associated with neurologic function. Type II interferon deficiency resulted in colonization of the brain by Brucella, but mice lacking both type I and type II interferon signaling more rapidly developed clinical signs of neurobrucellosis, exhibited hippocampal neuronal loss, and had higher levels of Brucella in their brains than mice lacking type II interferon signaling alone. Collectively, these findings indicate ILCs and interferons play an important role in prevention of focal complications during Brucella infection, and that mice with deficiencies in ILCs or interferons can be used to study pathogenesis of neurobrucellosis.

Single-cell landscape dissecting the transcription and heterogeneity of innate lymphoid cells in ischemic heart.

Until now, few articles have revealed the potential roles of innate lymphoid cells (ILCs) in cardiovascular diseases. However, the infiltration of ILC subsets in ischemic myocardium, the roles of ILC subsets in myocardial infarction (MI) and myocardial ischemia-reperfusion injury (MIRI) and the related cellular and molecular mechanisms have not been described with a sufficient level of detail. In the current study, 8-week-old male C57BL/6J mice were divided into three groups: MI, MIRI and sham group. Single-cell sequencing technology was used to perform dimensionality reduction clustering of ILC to analyze the ILC subset landscape at a single-cell resolution, and finally flow cytometry was used to confirm the existence of the new ILC subsets in different disease groups. Five ILC subsets were found, including ILC1, ILC2a, ILC2b, ILCdc and ILCt. It is worth noting that ILCdc, ILC2b and ILCt were identified as new ILC subclusters in the heart. The cellular landscapes of ILCs were revealed and signal pathways were predicted. Furthermore, pseudotime trajectory analysis exhibited different ILC statuses and traced related gene expression in normal and ischemic conditions. In addition, we established a ligand-receptor-transcription factor-target gene regulatory network to disclose cell communications among ILC clusters. Moreover, we further revealed the transcriptional features of the ILCdc and ILC2a subsets. Finally, the existence of ILCdc was confirmed by flow cytometry. Collectively, by characterizing the spectrums of ILC subclusters, our results provide a new blueprint for understanding ILC subclusters' roles in myocardial ischemia diseases and further potential treatment targets.

Innate lymphoid cells and interferons limit neurologic complications of Brucellosis.

Abstract Brucellosis is a globally significant zoonotic disease. Human brucellosis patients develop flu-like symptoms and focal complications including arthritis and neurobrucellosis. The purpose of our study was to uncover the role of innate lymphoid cells (ILCs) in the pathogenesis of focal brucellosis. After footpad infection, we found NK cells and ILC1 cells both limit joint colonization by Brucella. Mice lacking NK cells, and in particular mice lacking all ILCs also developed marked arthritis after footpad infection. Following pulmonary infection, mice lacking adaptive immune cells and ILCs developed arthritis, neurologic complications, and meningitis. Adaptive immune cells and ILCs both limited colonization of the brain by Brucella following pulmonary infection. Transcriptional analysis of Brucella-infected brains revealed marked upregulation of genes associated with inflammation and interferon responses, as well as downregulation of genes associated with neurologic function. Type II interferon deficiency resulted in colonization of the brain by Brucella, but mice lacking both type I and type II interferon signaling more rapidly developed clinical signs of neurobrucellosis, exhibited hippocampal neuronal loss, and had higher levels of Brucella in their brains than mice lacking type II interferon signaling alone. Collectively, our findings indicate ILCs and interferons play an important role in prevention of focal complications during Brucella infection, and that mice with deficiencies in ILCs or interferons can be used to study pathogenesis of neurobrucellosis. Supported by grants from NIH (T32 OD011126-4, R21 AI153074-02)

Potential Role of Innate Lymphoid Cells in the Pathogenesis and Treatment of Skin Diseases.

Group 2 innate lymphoid cells (ILC2s) are lymphoid cells that are resident in mucosal tissues, especially the skin, which, once stimulated by epithelial cell-derived cytokines, release IL-5, IL-13, and IL-4, as the effectors of type 2 immune responses. This research aims to evaluate the role of ILC2s in the pathogenesis of skin diseases, with a particular focus on inflammatory cutaneous disorders, in order to also elucidate potential therapeutic perspectives. The research has been conducted in articles, excluding reviews and meta-analyses, on both animals and humans. The results showed that ILC2s play a crucial role in the pathogenesis of systemic skin manifestations, prognosis, and severity, while a potential antimelanoma role is emerging from the new research. Future perspectives could include the development of new antibodies targeting or stimulating ILC2 release. This evidence could add a new therapeutic approach to inflammatory cutaneous conditions, including allergic ones.

The Roles of Innate Lymphoid Cells in the Gastric Mucosal Immunology and Oncogenesis of Gastric Cancer

Innate lymphoid cells (ILCs) are a group of innate immune cells that have garnered considerable attention due to their critical roles in regulating immunity and tissue homeostasis. They are particularly abundant in the gastrointestinal tract, where they have been shown to interact with commensal bacteria, pathogens, and other components of the local microenvironment to influence host immune responses to infection and oncogenesis. Their tissue-residency properties enable gastric ILCs a localized and rapid response to alert and stress, which indicates their key potential in regulating immunosurveillance. In this review, we discuss the current understanding of the role of ILCs in the gastric mucosa, with a focus on their interactions with the gastric microbiota and Helicobacter pylori and their contributions to tissue homeostasis and inflammation. We also highlight recent findings on the involvement of ILCs in the pathogenesis of gastric cancer and the implications of targeting ILCs as a therapeutic approach. Overall, this review provides an overview of the diverse functions of ILCs in gastric mucosa and highlights their potential as targets for future therapies for gastric cancer.

Evaluation of Innate Lymphoid Cells (ILCs) Population in the Mouse Model of Colorectal Cancer.

Innate Lymphoid Cells (ILCs) promote tissue homeostasis, contribute to the immune defense mechanisms, and play important roles in the initiation of immune responses and chronic inflammation. To understand the roles of innate lymphoid cells in the pathophysiology of colorectal cancer (CRC) in the mouse model. CRC was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS) in Balb/c mice (the chemically induced group=18 mice), or orthotopic injection of CT-26 cell line into the colon of another set of Balb/c mice (the orthotopic group=14mice). Normal saline was injected into 18 mice, as the sham group. After 80 days, the chemically induced group was divided into two subgroups, dysplasia (8 mice) and reparative change (10 mice), based on pathological examinations. The frequencies of ILC1, 2, and 3 were then measured in colon tissues using flow cytometry by four markers including an anti-mouse lineage cocktail (FITC anti-mCD3/FITC anti-mGr-1/FITC anti-mCD11b/ FITC anti-mCD45R (B220)/FITC anti-mTer-119), PE/Cy7 anti-mouse CD45, PE anti-mouse CD117 (c-kit), and APC anti-mouse IL-33 Rα (ST2). The total ILC population was significantly higher in the chemically induced reparative change compared with the sham group. ILC1 percentage in the chemically induced reparative change was significantly higher compared to those in the other three groups (Sham, chemically induced dysplasia and orthotopic dysplasia). The orthotopic dysplasia group showed more ILC3 percentage than the other groups. ILC1 and ILC3 subgroups increased significantly in reparative and dysplastic experimental CRC respectively. Thus ILC1 may have an inhibitory effect on tumor growth whereas ILC3 promotes tumor progression.

Immunologic Role of Innate Lymphoid Cells against Mycobacterial tuberculosis Infection.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), is one of the leading causes of mortality due to respiratory tract infections worldwide. Infection by M. tb involves activation of a type I immune response characteristic of T helper type 1 (Th1) lymphocytes, natural killer (NK) cells, Interleukin-12 (IL-12), and interferon (IFN)-γ, all of which stimulate the activation of macrophages and robust phagocytosis in order to prevent further infectious manifestations and systemic dissemination. Recent discoveries about innate lymphoid cells (ILCs) have provided further insight about how these cells participate within the protective immune response against M. tb infection and help boost the type I immune response. In order to clearly understand the mechanisms of M. tb infection and advance the efficacy of future treatment and prevention, we must first look at the individual functions each type of immune cell plays within this process, specifically ILCs. By review of the recent literature and current evidence, our group aims to summarize the characterization of the three major groups of ILCs, including NK cells, and analyze the role that each group of ILCs play in the infectious process against M. tb in order to provide a more comprehensive understanding of the host immune response. Equally, previous studies have also highlighted the effects of how administration of the Bacille Calmette-Guérin (BCG) vaccine influences the cells and cytokines of the immune response against M. tb. Our group also aims to highlight the effects that BCG vaccine has on ILCs and how these effects provide added protection against M. tb.

Crosstalk between epithelium, myeloid and innate lymphoid cells during gut homeostasis and disease.

The gut epithelium not only provides a physical barrier to separate a noxious outside from a sterile inside but also allows for highly regulated interactions between bacteria and their products, and components of the immune system. Homeostatic maintenance of an intact epithelial barrier is paramount to health, requiring an intricately regulated and highly adaptive response of various cells of the immune system. Prolonged homeostatic imbalance can result in chronic inflammation, tumorigenesis and inefficient antitumor immune control. Here we provide an update on the role of innate lymphoid cells, macrophages and dendritic cells, which collectively play a critical role in epithelial barrier maintenance and provide an important linkage between the classical innate and adaptive arm of the immune system. These interactions modify the capacity of the gut epithelium to undergo continuous renewal, safeguard against tumor formation and provide feedback to the gut microbiome, which acts as a seminal contributor to cellular homeostasis of the gut.

Innate Lymphoid Cells - Neglected Players in Multiple Sclerosis.

Multiple sclerosis (MS) is a highly debilitating autoimmune disease affecting millions of individuals worldwide. Although classically viewed as T-cell mediated disease, the role of innate lymphoid cells (ILC) such as natural killer (NK) cells and ILC 1-3s has become a focal point as several findings implicate them in the disease pathology. The role of ILCs in MS is still not completely understood as controversial findings have been reported assigning them either a protective or disease-accelerating role. Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that ILCs infiltrate the central nervous system (CNS), mediate inflammation, and have a disease exacerbating role by influencing the recruitment of autoreactive T-cells. Elucidating the detailed role of ILCs and altered signaling pathways in MS is essential for a more complete picture of the disease pathology and novel therapeutic targets. We here review the current knowledge about ILCs in the development and progression of MS and preclinical models of MS and discuss their potential for therapeutic applications.

Imbalance of circulating innate lymphoid cell subpopulations in patients with chronic kidney disease

Innate lymphoid cells (ILCs) are a newly identified heterogeneous family of innate immune cells. We conducted this study to investigate the frequency of circulating ILC subsets in various chronic kidney diseases (CKD). In DN, the proportion of total ILCs and certain ILC subgroups increased significantly. Positive correlations between proportion of total ILCs, ILC1s and body mass index, glycated hemoglobin were observed in DN. In LN, a significantly increased proportion of ILC1s was found in parallel with a reduced proportion of ILC2s. The proportions of total ILCs and ILC1s were correlated with WBC count and the level of C3. In all enrolled patients, the proportion of total ILCs and ILC1s was significantly correlated with the levels of ACR and GFR. In the present study, the proportion of circulating ILC subsets increased significantly in various types of CKD and correlated with clinico-pathological features, which suggests a possible role for ILCs in CKD.