Novel antigen-presenting cell imparts T-dependent tolerance to gut microbiota.

Establishing and maintaining tolerance to self-antigens or innocuous foreign antigens is vital for the preservation of organismal health. Within the thymus, medullary thymic epithelial cells (mTECs) expressing autoimmune regulator (AIRE) have a critical role in self-tolerance through deletion of autoreactive T cells and promotion of thymic regulatory T (T) cell development. Within weeks of birth, a separate wave of T cell differentiation occurs in the periphery upon exposure to antigens derived from the diet and commensal microbiota, yet the cell types responsible for the generation of peripheral T (pT) cells have not been identified.

Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Treg cells.

Regulatory T (Treg) cells expressing the transcription factor Foxp3 are an essential suppressive T cell lineage of dual origin: Foxp3 induction in thymocytes and mature CD4 T cells gives rise to thymic (tTreg) and peripheral (pTreg) Treg cells, respectively. While tTreg cells suppress autoimmunity, pTreg cells enforce tolerance to food and commensal microbiota. However, the role of Foxp3 in pTreg cells and the mechanisms supporting their differentiation remain poorly understood.

Regulatory T cells function in established systemic inflammation and reverse fatal autoimmunity.

The immunosuppressive function of regulatory T (T) cells is dependent on continuous expression of the transcription factor Foxp3. Foxp3 loss of function or induced ablation of T cells results in a fatal autoimmune disease featuring all known types of inflammatory responses with every manifestation stemming from T cell paucity, highlighting a vital function of T cells in preventing fatal autoimmune inflammation. However, a major question remains whether T cells can persist and effectively exert their function in a disease state, where a broad spectrum of inflammatory mediators can either inactivate T cells or render innate and adaptive pro-inflammatory effector cells insensitive to suppression.

Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells.

Intestinal health relies on the immunosuppressive activity of CD4 regulatory T (T) cells. Expression of the transcription factor Foxp3 defines this lineage, and can be induced extrathymically by dietary or commensal-derived antigens in a process assisted by a Foxp3 enhancer known as conserved non-coding sequence 1 (CNS1). Products of microbial fermentation including butyrate facilitate the generation of peripherally induced T (pT) cells, indicating that metabolites shape the composition of the colonic immune cell population.

Activation of Human Mucosal-Associated Invariant T Cells Induces CD40L-Dependent Maturation of Monocyte-Derived and Primary Dendritic Cells.

Mucosal-associated invariant T (MAIT) cells are innate T cells that recognize intermediates of the vitamin B2 biosynthetic pathway presented by the monomorphic MR1 molecule. It remains unclear whether, in addition to their cytolytic activity that is important in antimicrobial defense, MAIT cells have immune-modulatory functions that could enhance dendritic cell (DC) maturation. In this study, we investigated the molecular mechanisms dictating the interactions between human MAIT cells and DCs and demonstrate that human MAIT cells mature monocyte-derived and primary DCs in an MR1- and CD40L-dependent manner.