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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.
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.
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.
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.
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.
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.
Thymic regulatory T cells require IL-2 for their development. Robey and colleagues show that developing cells compete with pre-existing regulatory T cells for limiting amounts of IL-2 produced by antigen-bearing dendritic cells
Regulatory T cells (Treg cells) can suppress autoreactive immune responses in the periphery. Joost van Meerwijk and colleagues show that activated peripheral Treg cells can recirculate back to the thymus, where they can suppress further thymic Treg cell development.
A20 is a deubiquitinating enzyme that restrict inflammation by various mechanisms. Ma and colleagues show that A20 inhibits necroptosis by inhibiting the ubiquitination of RIPK3 and formation of the RIPK1-RIPK3 complex.
Fungal infection induces signaling downstream C-type lectin receptors through the activation of the tyrosine kinase Syk. Xiao and colleagues show that the phosphatase SHP-2 recruits Syk to dectin-1.
Eosinophils are commonly observed in solid tumors, but their role has remained uncertain. Hämmerling and colleagues show that activated eosinophils contribute to tumor eradication by altering tumor vasculature and increasing the infiltration of CD8+ T cells.
The transcriptional regulation of the differentiation of innate lymphoid cells remains incompletely characterized. Kaye and colleagues show that the transcriptional regulator TOX is required for the differentiation of common lymphoid progenitors into the innate lymphoid cell lineage.
The process of B cell differentiation into plasma cells involves dramatic cellular reprogramming. Corcoran and colleagues profile the transcriptome of all stages of B cell differentiation through to antibody-secreting plasma cells.
Methylation of DNA CpG motifs is modulated in part by the TET family of epigenetic regulators. Aifantis and colleagues show that loss of TET1 function biases hematopoiesis toward the B cell lineage and promotes hematopoietic malignancies.
Singer and colleagues show that let-7 microRNAs target Zbtb16 mRNA, which encodes the transcription factor PLZF, to modulate PLZF expression during the terminal differentiation of NKT cells into effector subsets.
Peripheral innate immunological signals can amplify adaptive immune responses. Cai and colleagues show that hypothalamicexposure to the cytokine TNF triggers a neural response that amplifies peripheral lymphocyte activation in the spleen and adipose tissues.
Mature naive B cells express membrane IgM and IgD B cell receptors. Jumaa and colleagues show that the hinge region of these regions confers differential responses to monovalent versus multivalent antigens and thereby influences B cell reactivity.
Fine-tuning of TLR7 signaling modulates innate inflammatory responses. Means and colleagues identify the receptor TREML4 as an essential positive regulator of TLR7 signaling during antiviral responses and autoimmunity.
Mutations in the gene encoding the helicase senataxin have well established associations with the neurodegenerative disease ALS. Marazzi et al. show that senataxin can also attenuate virus-triggered responses by controlling RNA polymerase activity at genes encoding antiviral molecules.