scholarly journals Islet-Resident Dendritic Cells and Macrophages in Type 1 Diabetes: In Search of Bigfoot’s Print

2021 ◽  
Vol 12 ◽  
Author(s):  
Henner Zirpel ◽  
Bart O. Roep
Keyword(s):  
Type 1 Diabetes ◽  
Dendritic Cells ◽  
Immune System ◽  
Current Knowledge ◽  
Treatment Options ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Future Research ◽  
Target Tissue

The classical view of type 1 diabetes assumes that the autoimmune mediated targeting of insulin producing ß-cells is caused by an error of the immune system. Malfunction and stress of beta cells added the target tissue at the center of action. The innate immune system, and in particular islet-resident cells of the myeloid lineage, could function as a link between stressed ß-cells and activation and recognition by the adaptive immune system. We survey the role of islet-resident macrophages and dendritic cells in healthy islet homeostasis and pathophysiology of T1D. Knowledge of islet-resident antigen presenting cells in rodents is substantial, but quite scarce in humans, in particular regarding dendritic cells. Differences in blood between healthy and diseased individuals were reported, but it remains elusive to what extend these contribute to T1D onset. Increasing our understanding of the interaction between ß-cells and innate immune cells may provide new insights into disease initiation and development that could ultimately point to future treatment options. Here we review current knowledge of islet-resident macrophages and dendritic cells, place these in context of current clinical trials, and guide future research.

scholarly journals Gene expression signatures of target tissues in type 1 diabetes, lupus erythematosus, multiple sclerosis, and rheumatoid arthritis

2021 ◽  
Vol 7 (2) ◽  
pp. eabd7600
Author(s):  
F. Szymczak ◽  
M. L. Colli ◽  
M. J. Mamula ◽  
C. Evans-Molina ◽  
D. L. Eizirik
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Type 1 Diabetes ◽  
Immune System ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Future Research ◽  
Target Tissue ◽  
Sequencing Data

Autoimmune diseases are typically studied with a focus on the immune system, and less attention is paid to responses of target tissues exposed to the immune assault. We presently evaluated, based on available RNA sequencing data, whether inflammation induces similar molecular signatures at the target tissues in type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. We identified confluent signatures, many related to interferon signaling, indicating pathways that may be targeted for therapy, and observed a high (>80%) expression of candidate genes for the different diseases at the target tissue level. These observations suggest that future research on autoimmune diseases should focus on both the immune system and the target tissues, and on their dialog. Discovering similar disease-specific signatures may allow the identification of key pathways that could be targeted for therapy, including the repurposing of drugs already in clinical use for other diseases.

scholarly journals The association between enteroviruses and type 1 diabetes

2012 ◽  
Vol 19 (3) ◽  
pp. 323-329
Author(s):  
Gabriela Florina Dale ◽  
Loredana Popa ◽  
Amorin Popa
Keyword(s):  
Type 1 Diabetes ◽  
Immune System ◽  
Viral Infection ◽  
Animal Studies ◽  
Human Studies ◽  
Target Tissue ◽  
Complex Interactions ◽  
Prevention And Treatment ◽  
Host Target

Abstract The hypothesis that under some circumstances enteroviral infections can lead to type1 diabetes (T1D) was proposed several decades ago, based initially on evidence fromanimal studies and sero-epidemiology. The mechanisms leading to the diseaseinvolve complex interactions between the virus, host target tissue (pancreas) and theimmune system. The following article is intended as a review of several recentinformation of the topic based on human studies that try to establish a connectionbetween a viral infection and Type 1 diabetes. Through understanding better thisassociation and it’s implications in the onset of T1D potential new ways ofprevention and treatment may emerge.

Antibody equivalent molecules of the innate immune system: parallels between innate and adaptive immune proteins

2010 ◽  
Vol 16 (3) ◽  
pp. 131-137 ◽  
Author(s):  
Nades Palaniyar
Keyword(s):  
Pattern Recognition ◽  
Immune System ◽  
Innate Immune System ◽  
Adaptive Immune System ◽  
Surfactant Protein ◽  
Innate Immune ◽  
Future Research ◽  
Surfactant Protein D ◽  
Adaptive Immune ◽  
Carbohydrate Arrays

Soluble pattern-recognition innate immune proteins functionally resemble the antibodies of the adaptive immune system. Two major families of such proteins are ficolins and collectins or collagenous lectins (e.g. mannose-binding lectin [MBL], surfactant proteins [SP-A and SP-D] and conglutinin). In general, subunits of ficolins and collectins recognize the carbohydrate arrays of their targets via globular trimeric carbohydrate-recognition domains (CRDs) whereas IgG, IgM and other antibody isotypes recognize proteins via dimeric antigen-binding domains (Fab). Considering the structure and functions of these proteins, ficolins and MBL are analogous to molecules with the complement activating functions of C1q and the target recognition ability of IgG. Although the structure of SP-A is similar to MBL, it does not activate the complement system. Surfactant protein-D and conglutinin could be considered as the collagenous non-complement activating giant IgMs of the innate immune system. Proteins such as peptidoglycan-recognition proteins, pentraxins and agglutinin gp-340/DMBT1 are also pattern-recognition proteins. These proteins may be considered as different isotypes of antibody-like molecules. Proteins such as defensins, cathelicidins and lactoferrins directly or indirectly alter microbes or microbial growth. These proteins may not be considered as antibodies of the innate immune system. Hence, ficolins and collectins could be considered as specialized ‘antibodies of the innate immune system’ instead of ‘ante-antibody’ innate immune molecules. The discovery, structure, functions and future research directions of many of these soluble proteins and receptors such as Toll-like and NOD-like receptors are discussed in this special issue of Innate Immunity.

scholarly journals Immune outcomes and safety of high-dose oral insulin as a primary prevention immunotherapy in young autoantibody-negative children at high genetic risk for type 1 diabetes

2020 ◽  
Author(s):  
Robin Assfalg ◽  
Jan Knoop ◽  
Kristi L. Hoffman ◽  
Markus Pfirrmann ◽  
Jose Maria Zapardiel-Gonzalo ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune System ◽  
Primary Prevention ◽  
Genetic Risk ◽  
Adaptive Immune System ◽  
Oral Insulin ◽  
Dependent Manner ◽  
Cell Responses ◽  
Adaptive Immune

AbstractBackgroundOral administration of antigen can induce immunological tolerance. Insulin is a key autoantigen in childhood type 1 diabetes with insulin autoimmunity often appearing in the first years of life. The aim of this study was to assess the safety and immunological effects of oral insulin immunotherapy as a primary prevention.MethodsA phase I/II randomized controlled trial (Clinicaltrials.govNCT02547519) was performed in 44 islet autoantibody-negative children aged 6 months to 2 years with familial and additional genetic risk for type 1 diabetes. Children were randomized 1:1 to daily insulin (7.5 mg with dose escalation to 67.5 mg) or placebo for 12 months. Hypoglycemia was a major safety measure. The primary immune efficacy outcome was an induction of antibody or T cell responses to oral insulin.ResultsOral insulin was well tolerated with no changes in metabolic variables. The primary immune outcome did not differ between treatment groups and responses were observed in both children who received insulin (55%) or placebo (67%). Responses were, however, modified by the type 1 diabetes INSULIN gene. Among children with a susceptible genotype, antibody responses to insulin were more frequent in insulin-treated (cumulative response, 75.8%) as compared to placebo-treated children (18.2%; P = 0.0085). Mechanistic studies identified microbiome changes that were related to INSULIN genotype and frequent treatment-independent inflammatory episodes that modified the in vitro T cell responses to insulin in children with susceptible INSULIN genotypes.ConclusionThe study demonstrated that oral insulin immunotherapy in young genetically at-risk children was safe and engaged the adaptive immune system in an INSULIN genotype-dependent manner, and linked inflammatory episodes to the activation of insulin-responsive T cells.One Sentence SummaryOral insulin given daily to very young children was safe and may engage the adaptive immune system in an INSULIN genotype-dependent manner.

scholarly journals Neutrophils—From Bone Marrow to First-Line Defense of the Innate Immune System

2021 ◽  
Vol 12 ◽  
Author(s):  
Richard Felix Kraus ◽  
Michael Andreas Gruber
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Current Knowledge ◽  
Immune Defense ◽  
Innate Immune ◽  
Human Organism ◽  
Polymorphonuclear Cells ◽  
Target Tissue ◽  
First Line

Neutrophils (polymorphonuclear cells; PMNs) form a first line of defense against pathogens and are therefore an important component of the innate immune response. As a result of poorly controlled activation, however, PMNs can also mediate tissue damage in numerous diseases, often by increasing tissue inflammation and injury. According to current knowledge, PMNs are not only part of the pathogenesis of infectious and autoimmune diseases but also of conditions with disturbed tissue homeostasis such as trauma and shock. Scientific advances in the past two decades have changed the role of neutrophils from that of solely immune defense cells to cells that are responsible for the general integrity of the body, even in the absence of pathogens. To better understand PMN function in the human organism, our review outlines the role of PMNs within the innate immune system. This review provides an overview of the migration of PMNs from the vascular compartment to the target tissue as well as their chemotactic processes and illuminates crucial neutrophil immune properties at the site of the lesion. The review is focused on the formation of chemotactic gradients in interaction with the extracellular matrix (ECM) and the influence of the ECM on PMN function. In addition, our review summarizes current knowledge about the phenomenon of bidirectional and reverse PMN migration, neutrophil microtubules, and the microtubule organizing center in PMN migration. As a conclusive feature, we review and discuss new findings about neutrophil behavior in cancer environment and tumor tissue.

scholarly journals LA RESPUESTA INMUNITARIA FRENTE AL VIRUS SARS-CoV-2

2020 ◽  
Vol 3 (9) ◽  
pp. 64-86
Author(s):  
SERGIO ROBERTO AGUILAR-RUIZ ◽  
FRANCISCO JAVIER SÁNCHEZ-PEÑA
Keyword(s):  
Immune System ◽  
Viral Entry ◽  
Immune Cells ◽  
Innate Immune System ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Adaptive Immune ◽  
Infected Cells ◽  
Systemic Pathology

The immune response against SARS-CoV-2 is similar to that against other viruses, where the innate immune system acts at early stages through the secretion of type 1 interferon (type 1 IFN), which prevents viral replication and the activation of natural killer (NK) cells. Later, the adaptive immune system acts through CD8+ cytotoxic T-lymphocytes and antibody production, which aim to destroy infected cells and block viral entry into cells. All the above leads to the elimination of the virus and mild symptomatology. However, in individuals with a weakened immune system, the viral infection spreads and leads to a potent inflammatory response, which leads to the recruitment of immune cells to the lungs, where they can cause severe pulmonary and even systemic pathology.

Immune mechanisms: innate immunity

2016 ◽  
Author(s):  
Troy Noordenbos ◽  
Dominique Baeten
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Signs And Symptoms ◽  
Innate Immune ◽  
Molecular Characteristics ◽  
Target Tissue ◽  
Hla B27 ◽  
Genetic Associations ◽  
Immune Mechanisms ◽  
Adaptive Immune

Innate immune mechanisms are strongly implied in the pathophysiology of spondyloarthritis (SpA). This chapter discusses available data on the role of the innate immune system in relation to HLA-B27, genetic associations, and the cellular and molecular characteristics of disease target tissue. Regarding the linkage with MCH-class I molecule HLA-B27, the chapter discusses the arthritogenic peptide hypothesis and three popular antigen-independent theories. The genetic architecture of the disease argues against a role for the adaptive immune system and identifies cytokine pathways, such as IL-1, TNF, and IL-23/IL-17. In experimental as well as in human SpA, the importance of these cytokine pathways are confirmed by effective reduction of signs and symptoms upon blockade of specific molecules. In-depth cellular and molecular analysis of the target tissue identifies a contribution of cells with strong innate features, rather than cells of the adaptive immune system.

scholarly journals 100 YEARS OF INSULIN: Arresting or curing type 1 diabetes: an elusive goal, but closing the gap

2021 ◽  
Vol 249 (2) ◽  
pp. T1-T11
Author(s):  
Pieter-Jan Martens ◽  
Conny Gysemans ◽  
Chantal Mathieu
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Adaptive Immune System ◽  
Future Research ◽  
Diabetic Patients ◽  
Technological Advances ◽  
Current Therapies

Type 1 diabetes is one of the most common chronic diseases in children and adolescents, but remains unpreventable and incurable. The discovery of insulin, already 100 years ago, embodied a lifesaver for people with type 1 diabetes as it allowed the replacement of all functions of the beta cell. Nevertheless, despite all technological advances, the majority of type 1 diabetic patients fail to reach the recommended target HbA1c levels. The disease-associated complications remain the true burden of affected individuals and necessitate the search for disease prevention and reversal. The recognition that type 1 diabetes is a heterogeneous disease with an etiology in which both the innate and adaptive immune system as well as the insulin-producing beta cells intimately interact, has fostered the idea that treatment to specific molecular or cellular characteristics of the patient groups will be needed. Moreover, robust and reliable biomarkers to detect type 1 diabetes in the early (pre-symptomatic) phases are wanted to preserve functional beta cell mass. The pitfalls of past therapeutics along with the perspectives of current therapies can open up the path for future research.

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