Dietary environmental factors shape the immune defense against Cryptosporidium infection.

Cryptosporidium is a leading cause of diarrheal-related deaths in children, especially in resource-poor settings. It also targets the immunocompromised, chronically infecting people living with HIV and primary immunodeficiencies. There is no vaccine or effective treatment.

Genetically encoded Runx3 and CD4 intestinal epithelial lymphocyte deficiencies link SKG mouse and human predisposition to spondyloarthropathy.

Disturbances in immune regulation, intestinal dysbiosis and inflammation characterize ankylosing spondylitis (AS), which is associated with RUNX3 loss-of-function variants. ZAP70 mutant (SKG) mice have reduced ZAP70 signaling, spondyloarthritis and ileitis. In small intestine, Foxp3 regulatory T cells (Treg) and CD4CD8ααTCRαβ intraepithelial lymphocytes (CD4-IEL) control inflammation.

Neuronal programming by microbiota regulates intestinal physiology.

Neural control of the function of visceral organs is essential for homeostasis and health. Intestinal peristalsis is critical for digestive physiology and host defence, and is often dysregulated in gastrointestinal disorders. Luminal factors, such as diet and microbiota, regulate neurogenic programs of gut motility, but the underlying molecular mechanisms remain unclear.

In silico identification and wet lab validation of novel cryptic B cell epitopes in ZnT8 zinc transporter autoantigen.

Zinc transporter 8 (ZnT8) is a novel immunodominant autoantigen, associated with Type-1 diabetes. A non-synonymous polymorphism (R325W) in its gene is associated with Type-2 diabetes. In this study, we performed an in silico B cell epitope prediction followed by wetlab validation of ZnT8.

The Environmental Sensor AHR Protects from Inflammatory Damage by Maintaining Intestinal Stem Cell Homeostasis and Barrier Integrity.

The epithelium and immune compartment in the intestine are constantly exposed to a fluctuating external environment. Defective communication between these compartments at this barrier surface underlies susceptibility to infections and chronic inflammation. Environmental factors play a significant, but mechanistically poorly understood, role in intestinal homeostasis.

Autoimmune-Mediated Thymic Atrophy Is Accelerated but Reversible in RelB-Deficient Mice.

Polymorphisms impacting thymic function may decrease peripheral tolerance and hasten autoimmune disease. The NF-κB transcription factor subunit, RelB, is essential for the development and differentiation of medullary thymic epithelial cells (mTECs): RelB-deficient mice have reduced thymic cellularity and markedly fewer mTECs, lacking AIRE. The precise mechanism of this mTEC reduction in the absence of RelB is unclear.

RelB-Deficient Dendritic Cells Promote the Development of Spontaneous Allergic Airway Inflammation.

RelB is a member of the NF-κB family, which is essential for dendritic cell (DC) function and maturation. However, the contribution of RelB to the development of allergic airway inflammation (AAI) is unknown. Here, we identify a pivotal role for RelB in the development of spontaneous AAI that is independent of exogenous allergen exposure.

Immunomodulatory liposomes targeting liver macrophages arrest progression of nonalcoholic steatohepatitis.

Objective: Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic macrophage inflammation, steatosis and fibrosis. Liposomes injected intravenously passively target hepatic myeloid cells and have potential to deliver immunomodulatory compounds and treat disease. We investigated targeting, delivery, immunomodulation and efficacy of liposomes in mice with diet-induced NASH.

Deletion of Wntless in myeloid cells exacerbates liver fibrosis and the ductular reaction in chronic liver injury.

Background: Macrophages play critical roles in liver regeneration, fibrosis development and resolution. They are among the first responders to liver injury and are implicated in orchestrating the fibrogenic response via multiple mechanisms. Macrophages are also intimately associated with the activated hepatic progenitor cell (HPC) niche or ductular reaction that develops in parallel with fibrosis.

Targeted delivery of curcumin for treating type 2 diabetes.

Type 2 diabetes is a chronic condition in which cells have reduced insulin signalling, leading to hyperglycemia and long-term complications, including heart, kidney and liver disease. Macrophages activated by dying or stressed cells, induce the transcription factor nuclear factor kappa-B leading to the production of pro-inflammatory cytokines including TNF and IL-6. These inflammatory macrophages in liver and adipose tissue promote insulin resistance, and medications which reduce inflammation and enhance insulin signalling improve glucose control.