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 Citrullination and PAD Enzyme Biology in Type 1 Diabetes – Regulators of Inflammation, Autoimmunity, and Pathology

2021 ◽  
Vol 12 ◽  
Author(s):  
Mei-Ling Yang ◽  
Fernanda M. C. Sodré ◽  
Mark J. Mamula ◽  
Lut Overbergh
Keyword(s):  
Rheumatoid Arthritis ◽  
Type 1 Diabetes ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Nod Mice ◽  
Neutrophil Extracellular Trap ◽  
Comprehensive Overview ◽  
General Role

The generation of post-translational modifications (PTMs) in human proteins is a physiological process leading to structural and immunologic variety in proteins, with potentially altered biological functions. PTMs often arise through normal responses to cellular stress, including general oxidative changes in the tissue microenvironment and intracellular stress to the endoplasmic reticulum or immune-mediated inflammatory stresses. Many studies have now illustrated the presence of ‘neoepitopes’ consisting of PTM self-proteins that induce robust autoimmune responses. These pathways of inflammatory neoepitope generation are commonly observed in many autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and type 1 diabetes (T1D), among others. This review will focus on one specific PTM to self-proteins known as citrullination. Citrullination is mediated by calcium-dependent peptidylarginine deiminase (PAD) enzymes, which catalyze deimination, the conversion of arginine into the non-classical amino acid citrulline. PADs and citrullinated peptides have been associated with different autoimmune diseases, notably with a prominent role in the diagnosis and pathology of rheumatoid arthritis. More recently, an important role for PADs and citrullinated self-proteins has emerged in T1D. In this review we will provide a comprehensive overview on the pathogenic role for PADs and citrullination in inflammation and autoimmunity, with specific focus on evidence for their role in T1D. The general role of PADs in epigenetic and transcriptional processes, as well as their crucial role in histone citrullination, neutrophil biology and neutrophil extracellular trap (NET) formation will be discussed. The latter is important in view of increasing evidence for a role of neutrophils and NETosis in the pathogenesis of T1D. Further, we will discuss the underlying processes leading to citrullination, the genetic susceptibility factors for increased recognition of citrullinated epitopes by T1D HLA-susceptibility types and provide an overview of reported autoreactive responses against citrullinated epitopes, both of T cells and autoantibodies in T1D patients. Finally, we will discuss recent observations obtained in NOD mice, pointing to prevention of diabetes development through PAD inhibition, and the potential role of PAD inhibitors as novel therapeutic strategy in autoimmunity and in T1D in particular.

Intestinale Dysbiose und Mikrobiomtransfer bei Autoimmunerkrankungen

2021 ◽  
Vol 3 (2) ◽  
pp. 73-74
Author(s):  
Irina Blumenstein
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Type 1 Diabetes ◽  
Celiac Disease ◽  
Autoimmune Diseases ◽  
Intestinal Microbiome ◽  
Healthy Controls ◽  
Rodent Models

Recent studies have shown that a number of common autoimmune diseases have perturbations of their intestinal microbiome (dysbiosis). These include: Celiac Disease (CeD), Multiple Sclerosis (MS), Rheumatoid Arthritis (RA), Sjogren’s Syndrome (SS), and Type 1 diabetes (T1D). All of these have intestinal microbiomes that are different from healthy controls. There have been numerous studies using animal models of single probiotics (monoclonal) or mixtures of probiotics (polyclonal) and even complete microbiota transfer (fecal microbial transfer-FMT) to inhibit or delay the onset of autoimmune diseases such as the aforementioned common ones. However, proportionally, fewer clinical trials have utilized monoclonal therapies or FMT than polyclonal therapies for treating autoimmune diseases, even though bacterial mono-therapies do inhibit the development of autoimmune diseases and/or delay the onset of autoimmune diseases in rodent models of those autoimmune diseases. In this review then, we review the previously completed and currently ongoing clinical trials that are testing bacterial therapies (FMT, monoclonal, and polyclonal) to treat common autoimmune diseases and discuss the successes in using bacterial monotherapies to treat rodent models of these common autoimmune diseases.

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.

Cell-based Tolerogenic Therapy, Experience from Animal Models of Multiple Sclerosis, Type 1 Diabetes and Rheumatoid Arthritis

2017 ◽  
Vol 23 (18) ◽  
Author(s):  
Ivana Stojanovic ◽  
Mirjana Dimitrijevic ◽  
Marta Vives-Pi ◽  
Maria Jose Mansilla ◽  
Irma Pujol-Autonell ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Type 1 Diabetes ◽  
Animal Models

scholarly journals Solar Radiation and Vitamin D: Mitigating Environmental Factors in Autoimmune Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Gerry K. Schwalfenberg
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Inflammatory Bowel Disease ◽  
Vitamin D ◽  
Type 1 Diabetes ◽  
Autoimmune Disease ◽  
Solar Radiation ◽  
Inflammatory Bowel

This paper looks at the environmental role of vitamin D and solar radiation as risk reduction factors in autoimmune disease. Five diseases are considered: multiple sclerosis, type 1 diabetes, rheumatoid arthritis, autoimmune disease of the thyroid, and inflammatory bowel disease. Clinical relevant studies and factors that may indicate evidence that autoimmune disease is a vitamin D-sensitive disease are presented. Studies that have resulted in prevention or amelioration of some autoimmune disease are discussed. An example of the utility of supplementing vitamin D in an unusual autoimmune disease, idiopathic thrombocytic purpura, is presented.

scholarly journals Stem Cell Therapy and Regenerative Medicine in Autoimmune Diseases

2021 ◽  
Author(s):  
Bhuvaneshwari Sampath ◽  
Priyadarshan Kathirvelu ◽  
Kavitha Sankaranarayanan
Keyword(s):  
Stem Cell ◽  
Immune System ◽  
Regenerative Medicine ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Autoimmune Condition ◽  
Recent Trends

The role of immune system in our body is to defense against the foreign bodies. However, if the immune system fails to recognize self and non-self-cells in our body leads to autoimmune diseases. Widespread autoimmune diseases are rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, and more yet to be added to the list. This chapter discusses about how stem cell-based therapies and advancement of regenerative medicine endow with novel treatment for autoimmune diseases. Furthermore, in detail, specific types of stem cells and their therapeutic approach for each autoimmune condition along with their efficiency to obtain desired results are discussed. Ultimately, this chapter describes the recent trends in treating autoimmune diseases effectively using advanced stem cell research.

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.

Sign in / Sign up

Export Citation Format

Share Document