Volume 16 Issue 10, October 2015

Paradoxically, radiotherapy can reinforce immunosuppressive pathways that undermine anticancer immunosurveillance and treatment efficacy. Irradiation induces Langerhans cells to migrate from the skin to lymph nodes, where they stimulate regulatory T cells.

Immature B lymphocytes and T lymphocytes assemble antigen receptor–encoding genes in lineage- and developmental stage–specific fashion. New findings show that pre-B cells use specialized locus-specific epigenetic mechanisms to promote recombination of the locus encoding the immunoglobulin κ-chain (Igk) and κ-chain⁺ B cell development.

A unique guanosine-flanked Y-form DNA triggers innate cGAS-dependent responses that lead to upregulation of the production of type I interferons.

The transcriptional regulator TCF-1 marks rare progenitor cells in adult bone marrow that have lost the potential to develop into the lymphocyte lineage but can give rise to all innate lymphoid cell lineages.

Autophagy is an essential intracellular degradation process. Yoshimori and colleagues review the broad role of autophagy in immunological function.

Truncated reverse transcription of HIV RNA produces a single-stranded DNA intermediate with a unique Y-DNA stem-loop structure flanked by unpaired guanines. Schlee and colleagues show this Y-DNA activates cGAS to elicit the production of type I interferon.

The role of the stress-induced transcription factor ATF7 in immunity is largely unknown. Ishii and colleagues show that ATF7 represses select innate immunity–related genes, but activity is downregulated during the induction of macrophage memory.

The cellular and molecular events that drive early innate lymphoid cell (ILC) development remain poorly understood. Bhandoola and colleagues used a reporter mouse to identify a new subset of early ILC progenitors (EILPs) that express high amounts of TCF-1.

T cells are normally dependent on TCR stimulation to be activated. Guo and colleagues now show that memory type 2 helper T cells can respond to interleukin 33 elicited by helminth infection in an TCR-independent way to induce eosinophilic inflammation.

Treatment with ionizing radiation can lead to the accumulation of tumor-infiltrating T_reg cells. Merad and colleagues show that Langherans cells resist ionizing radiation via expression of p21 and potentiate the generation and accumulation of T_reg cells.

In the thymus, low-affinity T cell antigen receptor (TCR) engagement facilitates positive selection of the T cell repertoire. Takahama and colleagues now show TCR responsiveness of mature CD8⁺ T cells is fine-tuned by their affinity for positively selecting peptides in the thymus.

The molecular mechanisms that lead to T_H9 differentiation remain unclear. Chen and colleagues show that TGF-β- and IL-4-induced downregulation of the transcriptional repressor Id3 is required for T_H9 differentiation.

Tcra and Tcrd segments are embedded within a single locus but undergo distinct temporal rearrangements. Krangel and colleagues show that chromatin looping mediated by CTCF regulates the availability of variable gene segments to the RAG recombinase.

V(D)J recombination is developmentally regulated and occurs at restricted sites within the genome. Clark and colleagues show that the histone reader BRWD1 is required for precise positioning of nucleosomes and targeting of RAG recombinase proteins within the Igk locus.