The multifaceted roles of Bcl11b in thymic and peripheral T cells: impact on immune diseases

Abstract

The transcription factor Bcl11b is expressed in all T cell subsets and progenitors, starting from the DN2 stage of T cell development, and it regulates critical processes implicated in the development, function, and survival of many of these cells. Among the common roles of Bcl11b in T cell progenitors and mature T cell subsets are the repression of the innate genetic program and, to some extent, expression maintenance of TCR-signaling components. However, Bcl11b also has unique roles in specific T cell populations, suggesting that its functions depend on cell type and activation state of the cell. In this article, we provide a comprehensive review of the roles of Bcl11b in progenitors, effector T cells, regulatory T cells, and invariant NKT cells, as well as its impact on immune diseases. While emphasizing common themes, including some that might be extended to skin and neurons, we also describe the control of specific functions in different T cell subsets.

Figure 1. Roles of Bcl11b in thymic and peripheral T cells

Thymic developmental stages are indicated as double negative (DN1–DN4), double positive (DP) and single positive (SP). Specific T cell populations are indicated as invariant natural killer T (iNKT) cells, natural Treg (nTreg), inducible (iTreg) cells, CD4⁺ T, Th17, CD8⁺ T cells and cytotoxic T lymphocytes (CTL). T cell populations and processes in which Bcl11b plays a role are shown in red. Functions controlled by Bcl11b in each developmental stage or T cell subsets are indicated.