News & Views in 2015

Low availability of glucose in tumors negatively affects the activity of tumor-infiltrating T cells. Loss of T cell function under these conditions is mediated by the microRNAs miR-101 and miR-26a, which target expression of the methytransferase EZH2 and thereby diminish the expression of anti-tumor cytokines.

Understanding cytotoxic T cells has been a major focus of immunology research for decades. Proteomic profiling of these cells now brings them into unprecedented and revealing focus.

Immune responses are characterized by the concerted actions of both effector mechanisms and regulatory mechanisms. Signaling via the transcription factor STAT1 downstream of receptors for interferons and interleukin 27 (IL-27) can suppress type 2 immune responses induced by group 2 innate lymphoid cells (ILCs).

Small, soluble, ubiquitous ligands are difficult to visualize. Schwab and colleagues have created a functional receptor reporter that gauges the in vivo concentration, location and biological action of sphingolipids.

The transcription factor Nr4a1 can negatively regulate norepinephrine production in the context of neuroinflammation and thereby prevent the ensuing neuroinflammatory cascade in a mouse model of experimental autoimmune encephalomyelitis.

Mitochondria can contribute to an increase in the amount of phagosomal reactive oxygen species and thereby promote the effective killing of bacteria. Study of mice deficient in Mst1 and Mst2 reveals a role for these kinases in recruiting mitochondria to phagosomes.

Docking of T cell antigen receptors (TCRs) engaging complexes of peptide and major histocompatibility complex has shown the same diagonal orientation and polarity. A new study demonstrating that TCRs from regulatory T cells bind with reversed polarity challenges this dogma.

The T_H17 subset of helper T cells drives emphysema in smokers, but how these cells are elicited remains unknown. A study now links the microRNA miR-22 and the histone deacetylase HDAC4 to regulation of the activation of antigen-presenting cells after exposure to smoke.

The RNA endonuclease Drosha is required for myelopoiesis by its direct cleavage of stem-loop structures in mRNAs encoding Myl9 and Todr1.

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.

Paneth cell dysfunction has been linked to Crohn's disease. Nod2 and LRRK2, two genetic susceptibility factors for this disease, are now shown to have a role in regulating the sorting of lysozyme in Paneth cells and its secretion into the crypt space and, ultimately, in maintenance of the intestinal barrier.

Follicular helper T cells (T_FH cells) differentiate from naive T cells, but the picture of this differentiation process remains incomplete. Two studies now identify the related transcriptional regulators TCF-1 and LEF-1 as important early participants in this process.

A previously unknown function for T_H17 cell–derived IL-26 as a direct antimicrobial agent and activator of DNA-sensing innate immunity is now reported.

Intrathymic expression of self antigens is key for central tolerance. RNA-sequencing analysis of tissue-restricted antigens in individual medullary thymic epithelial cells reveals co-ordination in the gene-expression patterns that ensures effective self-representation for the production of self-tolerant T cells.

Targeted deletion of the transcription factor XBP1 in hematopoietic stem cells selectively prevents eosinophil maturation in the bone marrow without affecting other lineages of the immune system.

Fat-associated lymphoid clusters (FALCs) are non-classical secondary lymphoid organs of the body cavities. The formation and maturation of FALCs are driven by tumor-necrosis factor and are further enhanced by invariant natural killer T cells.

As the cytosolic guardian for many microbial and sterile inflammatory insults, NLRP3 is best appreciated for its innate immunological role mediating inflammasome activation. Now NLRP3 debuts as a transcription factor key for T_H2 polarization.