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Cell Aug 2018Innate lymphoid cells (ILCs) are lymphocytes that do not express the type of diversified antigen receptors expressed on T cells and B cells. ILCs are largely... (Review)
Review
Innate lymphoid cells (ILCs) are lymphocytes that do not express the type of diversified antigen receptors expressed on T cells and B cells. ILCs are largely tissue-resident cells and are deeply integrated into the fabric of tissues. The discovery and investigation of ILCs over the past decade has changed our perception of immune regulation and how the immune system contributes to the maintenance of tissue homeostasis. We now know that cytokine-producing ILCs contribute to multiple immune pathways by, for example, sustaining appropriate immune responses to commensals and pathogens at mucosal barriers, potentiating adaptive immunity, and regulating tissue inflammation. Critically, the biology of ILCs also extends beyond classical immunology to metabolic homeostasis, tissue remodeling, and dialog with the nervous system. The last 10 years have also contributed to our greater understanding of the transcriptional networks that regulate lymphocyte commitment and delineation. This, in conjunction with the recent advances in our understanding of the influence of local tissue microenvironments on the plasticity and function of ILCs, has led to a re-evaluation of their existing categorization. In this review, we distill the advances in ILC biology over the past decade to refine the nomenclature of ILCs and highlight the importance of ILCs in tissue homeostasis, morphogenesis, metabolism, repair, and regeneration.
Topics: Adaptive Immunity; Animals; B-Lymphocytes; Cytokines; Homeostasis; Humans; Hypothalamo-Hypophyseal System; Immunity, Innate; Inflammation; Killer Cells, Natural; Lymphocytes; Mice; Phenotype; Pituitary-Adrenal System; Regeneration; T-Lymphocytes
PubMed: 30142344
DOI: 10.1016/j.cell.2018.07.017 -
Nature Reviews. Immunology Nov 2022More than a decade ago, type 2 innate lymphoid cells (ILC2s) were discovered to be members of a family of innate immune cells consisting of five subsets that form a... (Review)
Review
More than a decade ago, type 2 innate lymphoid cells (ILC2s) were discovered to be members of a family of innate immune cells consisting of five subsets that form a first line of defence against infections before the recruitment of adaptive immune cells. Initially, ILC2s were implicated in the early immune response to parasitic infections, but it is now clear that ILC2s are highly diverse and have crucial roles in the regulation of tissue homeostasis and repair. ILC2s can also regulate the functions of other type 2 immune cells, including T helper 2 cells, type 2 macrophages and eosinophils. Dysregulation of ILC2s contributes to type 2-mediated pathology in a wide variety of diseases, potentially making ILC2s attractive targets for therapeutic interventions. In this Review, we focus on the spectrum of ILC2 phenotypes that have been described across different tissues and disease states with an emphasis on human ILC2s. We discuss recent insights in ILC2 biology and suggest how this knowledge might be used for novel disease treatments and improved human health.
Topics: Humans; Immunity, Innate; Lymphocytes; Th2 Cells
PubMed: 35354980
DOI: 10.1038/s41577-022-00704-5 -
Journal For Immunotherapy of Cancer Dec 2022The immunogenic nature of metastatic colorectal cancer (CRC) with high microsatellite instability (MSI-H) underlies their responsiveness to immune checkpoint blockade...
BACKGROUND
The immunogenic nature of metastatic colorectal cancer (CRC) with high microsatellite instability (MSI-H) underlies their responsiveness to immune checkpoint blockade (ICB). However, resistance to ICB is commonly observed, and is associated with the presence of peritoneal-metastases and ascites formation. The mechanisms underlying this site-specific benefit of ICB are unknown.
METHODS
We created a novel model for spontaneous multiorgan metastasis in MSI-H CRC tumors by transplanting patient-derived organoids (PDO) into the cecum of humanized mice. Anti-programmed cell death protein-1 (PD-1) and anti-cytotoxic T-lymphocytes-associated protein 4 (CTLA-4) ICB treatment effects were analyzed in relation to the immune context of primary tumors, liver metastases, and peritoneal metastases. Immune profiling was performed by immunohistochemistry, flow cytometry and single-cell RNA sequencing. The role of B cells was assessed by antibody-mediated depletion. Immunosuppressive cytokine levels (interleukin (IL)-10, transforming growth factor (TGF)b1, TGFb2, TGFb3) were determined in ascites and serum samples by ELISA.
RESULTS
PDO-initiated primary tumors spontaneously metastasized to the liver and the peritoneum. Peritoneal-metastasis formation was accompanied by the accumulation of ascites. ICB completely cleared liver metastases and reduced primary tumor mass but had no effect on peritoneal metastases. This mimics clinical observations. After therapy discontinuation, primary tumor masses progressively decreased, but peritoneal metastases displayed unabated growth. Therapy efficacy correlated with the formation of tertiary lymphoid structures (TLS)-containing B cells and juxtaposed T cells-and with expression of an interferon-γ signature together with the B cell chemoattractant CXCL13. B cell depletion prevented liver-metastasis clearance by anti-CTLA-4 treatment. Peritoneal metastases were devoid of B cells and TLS, while the T cells in these lesions displayed a dysfunctional phenotype. Ascites samples from patients with cancer with peritoneal metastases and from the mouse model contained significantly higher levels of IL-10, TGFb1, TGFb2 and TGFb3 than serum samples.
CONCLUSIONS
By combining organoid and humanized mouse technologies, we present a novel model for spontaneous multiorgan metastasis by MSI-H CRC, in which the clinically observed organ site-dependent benefit of ICB is recapitulated. Moreover, we provide empirical evidence for a critical role for B cells in the generation of site-dependent antitumor immunity following anti-CTLA-4 treatment. High levels of immunosuppressive cytokines in ascites may underlie the observed resistance of peritoneal metastases to ICB.
Topics: Mice; Animals; Immune Checkpoint Inhibitors; Transforming Growth Factor beta3; Peritoneum; Ascites; Peritoneal Neoplasms; Cytokines; Liver Neoplasms; Colorectal Neoplasms
PubMed: 36543378
DOI: 10.1136/jitc-2022-005345 -
The Korean Journal of Gastroenterology... Dec 2017Rumination syndrome is one of the functional gastroduodenal disorders. Effortless and repetitive regurgitation of recently ingested food from the stomach to the oral... (Review)
Review
Rumination syndrome is one of the functional gastroduodenal disorders. Effortless and repetitive regurgitation of recently ingested food from the stomach to the oral cavity followed by rechewing and reswallowing or spitting are the characteristic clinical features. This disorder is believed to be uncommon, but many patients with this disorder are overlooked by their physicians. Rumination might be caused by a reversal of the gastric contents through the esophagogastric junction, which is initiated by an increase in intragastric pressure. The characteristic symptoms are sufficient for the diagnosis of rumination syndrome. Postprandial high resolution esophageal impedance manometry can detect gastric pressurization exceeding 30 mmHg associated with the return of ingested material into the proximal esophagus, which is a pathognomonic finding of rumination syndrome. An extensive explanation of the condition and the underlying mechanism is the first step of the treatment of rumination syndrome. Behavioral therapy through diaphragmatic breathing is the mainstay of treatment. Further studies on the long term effects of biofeedback therapy as well as a proper strategy for refractory rumination syndrome are needed.
Topics: Behavior Therapy; Child; Electric Impedance; Esophagus; Feeding and Eating Disorders of Childhood; Humans; Sulpiride
PubMed: 29277089
DOI: 10.4166/kjg.2017.70.6.278 -
British Dental Journal Jul 2020
PubMed: 32651484
DOI: 10.1038/s41415-020-1859-1 -
Blood Jul 2014Innate lymphoid cells (ILCs) are lymphoid cells that do not express rearranged receptors and have important effector and regulatory functions in innate immunity and... (Review)
Review
Innate lymphoid cells (ILCs) are lymphoid cells that do not express rearranged receptors and have important effector and regulatory functions in innate immunity and tissue remodeling. ILCs are categorized into 3 groups based on their distinct patterns of cytokine production and the requirement of particular transcription factors for their development and function. Group 1 ILCs (ILC1s) produce interferon γ and depend on Tbet, group 2 ILCs (ILC2s) produce type 2 cytokines like interleukin-5 (IL-5) and IL-13 and require GATA3, and group 3 ILCs (ILC3s) include lymphoid tissue inducer cells, produce IL-17 and/or IL-22, and are dependent on RORγt. Whereas ILCs play essential roles in the innate immune system, uncontrolled activation and proliferation of ILCs can contribute to inflammatory autoimmune diseases. In this review, we provide an overview of the characteristics of ILCs in the context of health and disease. We will focus on human ILCs but refer to mouse studies if needed to clarify aspects of ILC biology.
Topics: Animals; Autoimmune Diseases; Cell Proliferation; Humans; Immunity, Innate; Inflammation; Lymphocytes; Mice; Nuclear Receptor Subfamily 1, Group F, Member 3
PubMed: 24778151
DOI: 10.1182/blood-2013-11-427781 -
Seminars in Immunology Nov 2022The family of innate lymphoid cells (ILCs) are composed of five canonical subsets, NK cells, ILC1, ILC2, ILC3 and Lymphoid tissue inducer cells. ILCs have important... (Review)
Review
The family of innate lymphoid cells (ILCs) are composed of five canonical subsets, NK cells, ILC1, ILC2, ILC3 and Lymphoid tissue inducer cells. ILCs have important functions in early stages of immune response towards infectious agents. ILCs are highly plastic enabling rapid modification of their functions dependent on the type of microbe and tissue environment to optimally counter these microbes. Data that still accumulate in a rapid pace indicate that these cells are also involved in immunity against tumor cells. Paradoxically ILC subsets have been shown to have tumor suppressing and tumor promoting activities. In this brief review we provide a snapshot of our current knowledge of characteristics and functions of tumor infiltrating ILC subsets and speculate on how these cells can be harnessed to mediate anti-tumor immunity.
Topics: Humans; Immunity, Innate; Lymphocytes; Killer Cells, Natural; T-Lymphocytes, Helper-Inducer; Neoplasms; Lymphoid Tissue; Lymphocyte Subsets
PubMed: 36306660
DOI: 10.1016/j.smim.2022.101654 -
Micromachines Jul 2018Liquid biopsies are easier to acquire patient derived samples than conventional tissue biopsies, and their use enables real-time monitoring of the disease through... (Review)
Review
Liquid biopsies are easier to acquire patient derived samples than conventional tissue biopsies, and their use enables real-time monitoring of the disease through continuous sampling after initial diagnosis, resulting in a paradigm shift to customized treatment according to the patient's prognosis. Among the various liquid biopsy samples, saliva is easily obtained by spitting or swab sucking without needing an expert for sample collection. In addition, it is known that disease related biomarkers that exist in the blood and have undergone extensive research exist in saliva even at a lower concentration than the blood. Thus, interest in the use of saliva as a liquid biopsy has increased. In this review, we focused on the salivary exosome and cell-free DNA (cfDNA) among the various biomarkers in saliva. Since the exosome and cfDNA in saliva are present at lower concentrations than the biomarkers in blood, it is important to separate and concentrate them before conducting down-stream analyses such as exosome cargo analysis, quantitative polymerase chain reaction (qPCR), and sequencing. However, saliva is difficult to apply directly to microfluidics-based systems for separation because of its high viscosity and the presence of various foreign substances. Therefore, we reviewed the microfluidics-based saliva pretreatment method and then compared the commercially available kit and the microfluidic chip for isolation and enrichment of the exosome and cfDNA in saliva.
PubMed: 30424273
DOI: 10.3390/mi9070340 -
Journal of Eating Disorders 2016This systematic review is an evaluation of the empirical literature relating to the disordered eating behaviour Chew and Spit (CHSP). Current theories postulate that... (Review)
Review
BACKGROUND
This systematic review is an evaluation of the empirical literature relating to the disordered eating behaviour Chew and Spit (CHSP). Current theories postulate that CHSP is a symptom exhibited by individuals with recurrent binge eating and Bulimia Nervosa.
AIMS
The review aimed to identify and critically assess studies that have examined the distribution of CHSP behaviour, its relationship to eating disorders, its physical and psychosocial consequences and treatment.
METHODS
A systematic database search with broad inclusion criteria, dated to January 2016 was conducted. Data were extracted by two authors and papers appraised for quality using a modified Downs and Black Quality Index.
RESULTS
Nine studies met the inclusion criteria. All were of clinical samples and majority (n = 7) were of low quality. The pathological action of chewing food but not swallowing was reported more often in those with restrictive type eating disorders, such as Anorexia Nervosa, than binge eating type disorders. CHSP also was reported to be an indicator of overall severity of an eating disorder and to appear more often in younger individuals. No studies of treatment were found.
CONCLUSIONS
Conclusions were limited due to the low quality and small numbers of studies based on clinical samples only. Further research is needed to address gaps in knowledge regarding the physiological, psychological, social, socioeconomic impact and treatment for those engaging in CHSP.
PubMed: 27555914
DOI: 10.1186/s40337-016-0115-1