METTL14-dependent mA modification controls iNKT cell development and function.

N-methyladenosine (mA), the most common form of RNA modification, controls CD4 T cell homeostasis by targeting the IL-7/STAT5/SOCS signaling pathways. The role of mA modification in unconventional T cell development remains unknown. Using mice with T cell-specific deletion of RNA methyltransferase METTL14 (T-Mettl14), we demonstrate that mA modification is indispensable for iNKT cell homeostasis.

Tolerogenic Immune-Modifying Nanoparticles Encapsulating Multiple Recombinant Pancreatic β Cell Proteins Prevent Onset and Progression of Type 1 Diabetes in Nonobese Diabetic Mice.

Type 1 diabetes (T1D) is an autoimmune disease characterized by T and B cell responses to proteins expressed by insulin-producing pancreatic β cells, inflammatory lesions within islets (insulitis), and β cell loss. We previously showed that Ag-specific tolerance targeting single β cell protein epitopes is effective in preventing T1D induced by transfer of monospecific diabetogenic CD4 and CD8 transgenic T cells to NOD. mice.

CD1-Restricted T Cells in Inflammatory Skin Diseases.

Autoimmunity results from the breaking of immune tolerance, leading to inflammation and pathology. Although well studied in the conventional T-cell field, the role of nonconventional T cells in autoimmunity is less understood. CD1-restricted T cells recognize lipid antigens rather than peptide antigens and have been implicated in various autoimmune skin conditions, including psoriasis and atopic dermatitis.

Type II Natural Killer T Cells Contribute to Protection Against Systemic Methicillin-Resistant Infection.

Methicillin-resistant (SA) bacteremia is responsible for over 10,000 deaths in the hospital setting each year. Both conventional CD4 T cells and γδ T cells play protective roles in SA infection through secretion of IFN-γ and IL-17. However, the role of other unconventional T cells in SA infection is largely unknown.

Group 1 CD1-restricted T cells contribute to control of systemic Staphylococcus aureus infection.

Staphylococcus aureus (SA) is the causative agent of both skin/soft tissue infections as well as invasive bloodstream infections. Though vaccines have been developed to target both humoral and T cell-mediated immune responses against SA, they have largely failed due to lack of protective efficacy. Group 1 CD1-restricted T cells recognize lipid rather than peptide antigens.

USP22 controls iNKT immunity through MED1 suppression of histone H2A monoubiquitination.

The ubiquitin pathway has been shown to regulate iNKT cell immunity, but the deubiquitinase involved in this process has not been identified. Herein we found that ubiquitin-specific peptidase 22 (USP22) is highly expressed in iNKT cells during their early developmental stage 1. USP22 deficiency blocked the transition from stage 1 to 2 during iNKT cell development in a cell-intrinsic manner.

Linking CD1-Restricted T Cells With Autoimmunity and Dyslipidemia: Lipid Levels Matter.

Dyslipidemia, or altered blood lipid content, is a risk factor for developing cardiovascular disease. Furthermore, several autoimmune diseases, including systemic lupus erythematosus, psoriasis, diabetes, and rheumatoid arthritis, are correlated highly with dyslipidemia. One common thread between both autoimmune diseases and altered lipid levels is the presence of inflammation, suggesting that the immune system might act as the link between these related pathologies.