Immunoglobulin A Antibodies: From Protection to Harmful Roles.

Immunoglobulin A (IgA) is the most abundantly produced antibody in humans. IgA is a unique class of immunoglobulin due to its multiple molecular forms, and a defining difference between the two subclasses: IgA1 has a long hinge-region that is heavily O-glycosylated, whereas the IgA2 hinge-region is shorter but resistant to bacterial proteases prevalent at mucosal sites. IgA is essential for immune homeostasis and education.

Innate Immunity in Type 1 Diabetes.

Type 1 diabetes (T1D) results from the destruction of pancreatic β cells by the immune system, to which both pancreatic β-cell dysfunction and pathological activation of the immune system contribute. This paper is focused on understanding the modalities of this activation, and the genetic and environmental factors increasing its risk. Innate immunity has a critical role in the loss of self-tolerance and promotion of inflammation either directly using innate effector mechanisms or by providing activation signals to anti-islet adaptive autoimmunity.

Deficiency and altered phenotype of mucosal-associated invariant T cells in systemic sclerosis.

Objective: Systemic sclerosis is an autoimmune disease characterized by fibrosis of the skin and internal organs including the lung. Mucosal-associated invariant T cells are innate-like T lymphocytes able to produce various cytokines and cytotoxic mediators such as granzyme B. A large body of evidence supports a role of mucosal-associated invariant T cells in autoimmune disease but more recent reports suggest also a potential role in fibrotic conditions.

MAIT cells altered phenotype and cytotoxicity in lupus patients are linked to renal disease severity and outcome.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease in which circulating immune complexes can cause different types of glomerulonephritis, according to immune deposits and to the type of glomerular cell injury. Proliferative lesions represent the most severe form of lupus nephritis (LN) and often lead to kidney failure and death. Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells that recognize microbial-derived ligands from the riboflavin synthesis pathway.

Lymph node sharing is caring for pancreatic immunity.

Lymph nodes can be shared among several organs, notably in the gastrointestinal system. In this issue of Immunity, Brown et al. describe how pancreatic immunity is shaped by the mixing of different migratory dendritic cells issued from co-drainage from liver, pancreas, and duodenum.

Insulin resistance per se drives early and reversible dysbiosis-mediated gut barrier impairment and bactericidal dysfunction.

Objective: A common feature of metabolic diseases is their association with chronic low-grade inflammation. While enhanced gut permeability and systemic bacterial endotoxin translocation have been suggested as key players of this metaflammation, the mechanistic bases underlying these features upon the diabesity cascade remain partly understood.

Methods: Here, we show in mice that, independently of obesity, the induction of acute and global insulin resistance and associated hyperglycemia, upon treatment with an insulin receptor (IR) antagonist (S961), elicits gut hyperpermeability without triggering systemic inflammatory response.

MAIT cell alterations in adults with recent-onset and long-term type 1 diabetes.

Aims/hypothesis: Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes expressing an αβ T cell antigen receptor that recognises the MHC-related 1 molecule. MAIT cells are altered in children at risk for and with type 1 diabetes, and mouse model studies have shown MAIT cell involvement in type 1 diabetes development. Since several studies support heterogeneity in type 1 diabetes physiopathology according to the age of individuals, we investigated whether MAIT cells were altered in adults with type 1 diabetes.

MAIT cells, guardians of skin and mucosa?

Mucosal Associated Invariant T (MAIT) cells are evolutionary conserved innate-like T cells able to recognize bacterial and fungal ligands derived from vitamin B biosynthesis. These cells are particularly present in liver and blood but also populate mucosal sites including skin, oral, intestinal, respiratory, and urogenital tracts that are in contact with the environment and microbiota of their host. Growing evidence suggests important involvement of MAIT cells in safeguarding the mucosa against external microbial threats.

Gut mucosa alterations and loss of segmented filamentous bacteria in type 1 diabetes are associated with inflammation rather than hyperglycaemia.

Objective: Type 1 diabetes (T1D) is an autoimmune disease caused by the destruction of pancreatic β-cells producing insulin. Both T1D patients and animal models exhibit gut microbiota and mucosa alterations, although the exact cause for these remains poorly understood. We investigated the production of key cytokines controlling gut integrity, the abundance of segmented filamentous bacteria (SFB) involved in the production of these cytokines, and the respective role of autoimmune inflammation and hyperglycaemia.

Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity.

Immune system dysfunction is paramount in coronavirus disease 2019 (COVID-19) severity and fatality rate. Mucosal-associated invariant T (MAIT) cells are innate-like T cells involved in mucosal immunity and protection against viral infections. Here, we studied the immune cell landscape, with emphasis on MAIT cells, in cohorts totaling 208 patients with various stages of disease.

Role of MAIT cells in metabolic diseases.

MAIT cells are innate-like T cells that are enriched in mucosal sites and tissues including adipose tissue and liver. They play an important role in immunity against microbial pathogens. Recently, it has been reported that MAIT cells could also be important in metabolic diseases and can be involved in setting up and maintaining chronic inflammation.

Mucosal-associated invariant T cells promote inflammation and intestinal dysbiosis leading to metabolic dysfunction during obesity.

Obesity is associated with low-grade chronic inflammation promoting insulin-resistance and diabetes. Gut microbiota dysbiosis is a consequence as well as a driver of obesity and diabetes. Mucosal-associated invariant T cells (MAIT) are innate-like T cells expressing a semi-invariant T cell receptor restricted to the non-classical MHC class I molecule MR1 presenting bacterial ligands.

MAIT Cells in Type 1 Diabetes Mouse Models.

MAIT cells are unconventional T cells expressing a semi-invariant αβ TCR, and they recognize bacterial metabolites via the highly conserved MR1 protein. MAIT cells interact with gut microbiota and literature reports alterations of gut homeostasis in type 1 diabetes (T1D), suggesting the involvement of MAIT cells in T1D. Since NOD mice is a well-established mouse model of T1D, MAIT cells were studied in these mice to evaluate their potential involvement in disease development.

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition).

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells.

MAIT cells in metabolic diseases.

Background: Metabolic diseases represent a wide category of alterations affecting metabolism. These pathologies are notably marked by inflammation that implicates the immune system. Mucosal Associated Invariant (MAI)T cells are immune cells expressing a semi-invariant TCR able to recognize bacterial and fungal vitamin B metabolites.

Mucosal-associated invariant T cells and disease.

Mucosal-associated invariant T (MAIT) cells are unique innate-like T cells that bridge innate and adaptive immunity. They are activated by conserved bacterial ligands derived from vitamin B biosynthesis and have important roles in defence against bacterial and viral infections. However, they can also have various deleterious and protective functions in autoimmune, inflammatory and metabolic diseases.

Mucosal-associated invariant T (MAIT) cells are depleted and prone to apoptosis in cardiometabolic disorders.

The disruption of systemic immune homeostasis is a key mediator in the progression of cardiometabolic diseases (CMDs). We aimed to extend knowledge regarding the clinical relevance of CMD-associated variation of circulating mucosal-associated invariant T (MAIT) cell abundance and to explore underlying cellular mechanisms. We analyzed cross-sectional data from 439 participants of the Metagenomics in Cardiometabolic Diseases (MetaCardis) study, stratified into 6 groups: healthy control subjects and patients with metabolic syndrome (MS), obesity, type 2 diabetes mellitus (T2DM), and coronary artery disease (CAD) without, or with congestive heart failure (CAD-CHF).

Author Correction: Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes.

In the version of this Article originally published, the asterisks indicating statistical significance were missing from Supplementary Figure 6; the file with the correct figure is now available.

Mucosal-associated invariant T cells are a profibrogenic immune cell population in the liver.

Liver fibrosis is the common response to chronic liver injury, and leads to cirrhosis and its complications. Persistent inflammation is a driving force of liver fibrosis progression. Mucosal-associated invariant T (MAIT) cells are non-conventional T cells that display altered functions during chronic inflammatory diseases.

Mucosal-associated invariant T cells in autoimmune and immune-mediated diseases.

Autoimmune and inflammatory diseases have complex etiologies not fully understood. Both innate and adaptive immune cells are involved in the pathogenesis of these diseases. Mucosal-associated invariant T (MAIT) cells express an invariant TCRα chain (Vα7.

Cytotoxic and regulatory roles of mucosal-associated invariant T cells in type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction of pancreatic β-cells by the immune system that involves innate and adaptive immune cells. Mucosal-associated invariant T cells (MAIT cells) are innate-like T-cells that recognize derivatives of precursors of bacterial riboflavin presented by the major histocompatibility complex (MHC) class I-related molecule MR1. Since T1D is associated with modification of the gut microbiota, we investigated MAIT cells in this pathology.

Intestinal invalidation of the glucose transporter GLUT2 delays tissue distribution of glucose and reveals an unexpected role in gut homeostasis.

Objective: Intestinal glucose absorption is orchestrated by specialized glucose transporters such as SGLT1 and GLUT2. However, the role of GLUT2 in the regulation of glucose absorption remains to be fully elucidated.

Methods: We wanted to evaluate the role of GLUT2 on glucose absorption and glucose homeostasis after intestinal-specific deletion of GLUT2 in mice (GLUT2 mice).

IRF5 governs liver macrophage activation that promotes hepatic fibrosis in mice and humans.

Hepatic fibrosis arises from inflammation in the liver initiated by resident macrophage activation and massive leukocyte accumulation. Hepatic macrophages hold a central position in maintaining homeostasis in the liver and in the pathogenesis of acute and chronic liver injury linked to fibrogenesis. Interferon regulatory factor 5 (IRF5) has recently emerged as an important proinflammatory transcription factor involved in macrophage activation under acute and chronic inflammation.