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Memory TH2 cells are rapidly recruited to tissues after exposure to stimulatory ligands. McKenzie and colleagues demonstrate that ILC2s have an essential role in facilitating TH2 cell memory responses in lung, skin and gut.
Glucose availability is limiting in tumor environments. Zou and colleagues show that reduced glycolytic metabolism in T cells within tumors suppresses expression of the methyltransferase EZH2, which limits production of antitumor effector molecules and enhances T cell apoptosis.
The TCR-peptide-MHC interface is composed of conserved and diverse regions, but the relative contributions of each in shaping T cell recognition remain unclear. Garcia and colleagues show consistent germline interactions between TCR and MHC, but enough flexibility in the TCR-peptide-MHC interface to allow adjustment for different peptides.
The mechanisms that regulate the tissue-specific localization and functions of innate lymphoid cells are poorly understood. Xiong and colleagues find that CCR10+ innate lymphoid cells are selectively programmed in skin-draining lymph nodes for cutaneous homeostatic regulation.
Smoking can lead to emphysema. Corry and colleagues show that smoke and carbon black particles induce the microRNA miR-22 as a mediator that suppresses expression of the histone deacetylase HDAC4 and thereby promotes a chronic TH17 cell–dependent inflammatory response.
To date, structural analysis has demonstrated a highly consistent binding pattern of the TCR to the MHC molecule. Rossjohn and colleagues reveal the first structures of two human Treg cell TCRs and show that they bind with a reversed polarity to the MHC.
The enzyme Drosha is associated with the biogenesis of microRNA. Chong and colleagues identify a non- microRNA function for Drosha in dendritic cell development.
The metabolic requirements of T cells vary according to their functional state. Matarese and colleagues show that the most functionally active human regulatory T cells are highly glycolytic and that this directly controls expression of a distinct splice variant of the transcription factor Foxp3.
Mitochondria must be juxtaposed to phagosomes to supply reactive oxygen species for effective killing of microbes. Zhou and colleagues demonstrate that the kinases Mst1 and Mst2 are important for controlling this redistribution of mitochondria.
The transcriptional control of lineage commitment to various ILC subsets is incompletely understood. Yokoyama and colleagues show that Runx3 is essential for the normal development of ILC1 and ILC3 cells but not ILC2 cells.
Sumoylation regulates many cellular processes, but its role in TCR signaling remains unknown. Li and colleagues show that sumoylation of the kinase PKC-θ is required for the assembly of a mature immunological synapse.
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.
Treatment with ionizing radiation can lead to the accumulation of tumor-infiltrating Treg cells. Merad and colleagues show that Langherans cells resist ionizing radiation via expression of p21 and potentiate the generation and accumulation of Treg cells.
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.
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.
The molecular mechanisms that lead to TH9 differentiation remain unclear. Chen and colleagues show that TGF-β- and IL-4-induced downregulation of the transcriptional repressor Id3 is required for TH9 differentiation.
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.
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 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.