A20 Restrains Thymic Regulatory T Cell Development

A20 Restrains Thymic Regulatory T Cell Development

Maintaining immune tolerance requires the production of Foxp3-expressing regulatory T (Treg) cells in the thymus. Activation of NF-κB transcription factors is critically required for Treg cell development, partly via initiating Foxp3 expression. NF-κB activation is controlled by a negative feedback regulation through the ubiquitin editing enzyme A20, which reduces proinflammatory signaling in m...

A two-step process for thymic regulatory T cell development.

Recognition of self-antigens is required for regulatory T (Treg) cells to exert dominant tolerance. However, the mechanism by which self-reactive thymocytes are diverted into the Treg cell subset is unclear. To address this question, we looked for the immediate precursors to Treg cells within Foxp3(-)CD4+CD8(-) thymocytes. By using intrathymic transfer, we found that the CD25hi subset is highly...

Interleukin-23 Restrains Regulatory T Cell Activity to Drive T Cell-Dependent Colitis

Interleukin-23 (IL-23) is an inflammatory cytokine that plays a key role in the pathogenesis of several autoimmune and inflammatory diseases. It orchestrates innate and T cell-mediated inflammatory pathways and can promote T helper 17 (Th17) cell responses. Utilizing a T cell transfer model, we showed that IL-23-dependent colitis did not require IL-17 secretion by T cells. Furthermore, IL-23-in...

Thymic and Extrathymic T Cell Development

Thymic and extrathymic T cell development.

The majority of T cells located in peripheral blood, spleen and lymph nodes are dependent on the thymus for proper differentiation and function. Only a minority of T lymphocytes located in these lymphoid organs is thymic-independent. In contrast, a large number of thymus-independent T cells is present in the gut epithelium. This review deals with phenotypic and functional characteristics of T c...