Differential regulation of lung homeostasis and silicosis by the TAM receptors MerTk and Axl.

Introduction: TAM receptor-mediated efferocytosis plays an important function in immune regulation and may contribute to antigen tolerance in the lungs, a site with continuous cellular turnover and generation of apoptotic cells. Some studies have identified failures in efferocytosis as a common driver of inflammation and tissue destruction in lung diseases. Our study is the first to characterize the function of the TAM receptors, Axl and MerTk, in the innate immune cell compartment, cytokine and chemokine production, as well as the alveolar macrophage (AM) phenotype in different settings in the airways and lung parenchyma.

NF kappa B regulator Bcl3 controls development and function of classical dendritic cells required for resistance to Toxoplasma gondii.

The atypical IκB family member Bcl3 associates with p50/NF-κB1 or p52/NF-κB2 homodimers in the nucleus, and positively or negatively modulates transcription in a context-dependent manner. In mice lacking Bcl3 globally or specifically in CD11c+ cells, we previously reported that Toxoplasma gondii infection is uniformly fatal and is associated with an impaired Th1 immune response. Since Bcl3 expression in dendritic cells (DC) is pivotal for antigen presentation and since classical DCs (cDC) are major antigen presenting cells, we investigated the role of Bcl3 specifically in cDCs in vivo by crossing Zbtb46 cre mice with Bcl3flx/flx mice.

Constitutive activation of NF-κB during early bone marrow development results in loss of B cells at the pro-B-cell stage.

There is a considerable body of work exploring the role of NF-κB family of transcription factors in the maturation and functions of later stage B cells; however, their role in the earlier bone marrow stages of development is less well understood despite the demonstration that NF-κB activity is present at all early stages of B-cell development. To explore the consequences of early, B cell-targeted constitutive activation of both NF-κB pathways on B-cell development, we generated mice that have either or both. NF-κB pathways constitutively activated beginning in early pro-B cells.

Bcl-3 suppresses differentiation of RORγt regulatory T cells.

Regulatory T cells (Tregs) exert inhibitory function under various physiological conditions and adopt diverse characteristics following environmental cues. Multiple subsets of Tregs expressing master transcription factors of helper T cells such as RORγt, T-bet, Gata3 and PPARγ have been characterized, but the molecular mechanism governing the differentiation of these subsets remains largely unknown. Here we report that the atypical IκB protein family member Bcl-3 suppresses RORγt Treg accumulation.

The NF-κB regulator Bcl-3 restricts terminal differentiation and promotes memory cell formation of CD8+ T cells during viral infection.

Bcl-3 is an atypical member of the IκB family that acts in the nucleus to modulate transcription of many NF-κB targets in a highly context-dependent manner. Accordingly, complete Bcl-3-/- mice have diverse defects in both innate and adaptive immune responses; however, direct effects of Bcl-3 action in individual immune cell types have not been clearly defined. Here, we document a cell-autonomous role for Bcl-3 in CD8+ T cell differentiation during the response to lymphocytic choriomeningitis virus infection.