Volume 16 Issue 7, July 2015

Sirtuin-1 (Sirt1), a protein deacetylase known for its multiple cellular functions, including roles in metabolism, stress response and aging, is a post-translational modulator of autoimmune regulator (Aire) in central immunotolerance.

Dynamic control of DNA methylation in the Cd4 locus serves an important role in reinforcing the binary fate stability of helper and cytotoxic T cells.

Dendritic cell progenitors commit to a specific conventional dendritic cell fate earlier than previously thought, by initiating transcription-factor regulatory circuits unique to their subtype.

Deep-sequencing analyses of immunoglobulin variable-segment genes from antibody-secreting cells have allowed comparisons of conventional immunization responses to disease flares experienced by patients with systemic lupus erythematosus. Such analyses provide insight into B cell recruitment and differentiation processes yielding expanded clones that contribute to this complex autoimmune disease.

Gerlic and colleagues examine the role of cell death, particularly necroptosis, in inflammation, in the context of recent insights into the roles of the key necroptosis effector molecules RIPK1, RIPK3 and MLKL.

Epithelial surfaces are the main entry point for viruses and thus are important immunological sites. Diefenbach and colleagues show that the related cytokines IL-22 and IFN-λ act together in the control of enterovirus infection.

The transcription factors Batf3 and IRF8 are required for the development of CD8α⁺ conventional dendritic cells (cDCs). Murphy and colleagues characterize the Batf3-IRF8 interactions that allow differentiation toward CD8α⁺ cDCs.

The progenitor stage of commitment toward the conventional dendritic cell subsets and the transcriptional networks that control it remain poorly understood. Two articles from Ginhoux and colleagues and Murphy and colleagues offer insight into these processes.

Dendritic cells present exogenous antigens to T cells on MHC class I or MHC class II. Cresswell and colleagues show that the transcription factor TFEB inhibits exogenous antigen presentation by MHC class I and enhances presentation by MHC class II by promoting phagosomal acidification.

Dysfunction of the deacetylase Sirt1 has been associated with certain metabolic diseases. Abramson and colleagues show that Sirt1 has high expression in the thymus, where it deacetylates the transcriptional regulator Aire and is essential for Aire's ability to switch on the expression of tissue-specific genes.

Cd4 expression in helper and cytotoxic T cells is locked in by gene-expression programs that define lineage identity. Littman and colleagues define stage-specific methylation and demethylation events that regulate the heritable expression of Cd4.

Patients with systemic lupus erythematosus (SLE) experience flares of autoantibody secretion. Sanz and colleagues track the plasma cell repertoires of patients with SLE and find a sizeable polyclonal contribution by newly activated autoreactive B cells.

Secondary mutations can drive the transformation of pre-leukemic clones that carry ETV6-RUNX1 translocations. Müschen and colleagues show that repeated inflammatory episodes induce aberrant coexpression of the DNA recombinases RAG and AID to promote the development of acute lymphoblastic leukemia.

B lineage development requires the transcription factors E2A, EBF1, Foxo1 and Ikaros. Murre and colleagues show that these factors gain access to lineage-specific enhancer sites by the action of the chromatin remodeler Brg1.