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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.
How expression of tissue-restricted self-antigens (TRA) is coordinated in medullary thymic epithelial cells (mTECs) remains unclear. Steinmetz and colleagues use single-cell RNA-sequencing to describe clusters of co-expressed TRAs.
Recruitment of the kinase Zap70 to the T cell receptor (TCR) is essential for signal transduction. Lillemeier and colleagues show that the conformation of Zap70 controls TCR dwell time, which in turn controls Zap70 activity.
Mucosal immunity is influenced by commensal bacteria. Liu and colleagues show that commensals direct selective cargo sorting in Paneth cells through the cytosolic sensor NOD2 and the kinase LRRK2 to promote symbiosis.
How expression of tissue-restricted self antigens is coordinated in medullary thymic epithelial cells has remained unclear. Benoist and colleagues use single-cell RNA sequencing to identify clusters of co-expressed tissue-restricted antigens.
Follicular helper T cells (TFH cells) are specialized effector CD4+ T cells that help B cells develop germinal centers and memory. Crotty and colleagues show that the transcription factors LEF-1 and TCF-1 are required for early TFH differentiation.
Post-translational modifications regulate various signaling cascades downstream of the TCR. Knobeloch and colleagues show that the deubiquitinase USP8 is required for thymocyte development by interacting with the adaptor Gads upon TCR stimulation.
Follicular helper T cells (TFH cells) require the transcription factor Bcl-6 and are antagonized by the transcription factor Blimp1 (encoded by Prdm1). Lilin Ye and colleagues show that acute viral infection induces the transcription factor TCF-1, which promotes TFH differentiation by enhancing Bcl6 expression while suppressing that of Prdm1.
Recent studies have shown features of antigen-specific memory in mouse NK cells, but it is unclear whether this phenomenon also exists in primates. Barouch and colleagues provide evidence for robust, durable, antigen-specific NK cell memory induced in primates after infection or vaccination.
TH17 cells have important roles at mucosal surfaces in both health and disease. Gilliet and colleagues show that IL-26 is preferentially produced by human TH17 cells and that this cytokine has both alarmin and direct antimicrobial functions.
The precise factors that control effective memory formation by T cells are unclear. Kaech et al. demonstrate that regulatory T cell–produced IL-10 is critical for the generation of CD8+ memory cells.
The transcription factor XBP1 is associated with endoplasmic reticulum stress. Glimcher and colleagues show that XBP1 is expressed during eosinophil differentiation and is uniquely required for the production of granule proteins and eosinophil survival.
Interferon-γ (IFN-γ) primes macrophages to undergo proinflammatory activation. Ivashkiv and colleagues detail the translational and metabolic program triggered in human macrophages after IFN-γ treatment.
Secretory IgA (SIgA) shapes the gut microbial composition. Pabst and colleagues show that the IgA-secreting plasma cell repertoire, once established, is remarkably resilient to changes in microbial populations that occur upon infection or antibiotic treatment.
Fat-associated lymphoid clusters are lymphoid tissues that support B-1 cells. Caamaño and colleagues show that inflammation that elicits the cytokine TNF and activates natural killer cells contributes to the formation of these clusters in visceral fat.
Hematopoietic stem cells are held in check to maintain their functional activity throughout life. Qian and colleagues show that the transcriptional regulator Foxm1 maintains the quiescence and self-renewal capacity of these cells in vivo.
The receptor NLRP3 is central to the formation of inflammasomes in myeloid cells. Ghiringhelli and colleagues demonstrate that NLRP3 also serves an important inflammasome-independent role in CD4+ T cells, in which it helps coordinate TH2 differentiation.
Post-translational modification of chemokines such as CXCL10 can regulate their activity. Albert and colleagues demonstrate that the endogenous peptidase DPP4 cleaves CXCL10 and thereby interferes with T cell recruitment to tumors.
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.