Volume 16 Issue 9, September 2015

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.

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.

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.

Everyone and everything seems to go 'big data' these days. The task ahead will be to train young immunologists to formulate intelligent hypotheses using big data resources.

Billions of cells in the body die through apoptosis every day and are cleared by both professional and non-professional phagocytes. Arandjelovic and Ravichandran review how apoptotic cell clearance is critical for immune homeostasis.

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.

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.

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.

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.

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.

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.

T_H17 cells have important roles at mucosal surfaces in both health and disease. Gilliet and colleagues show that IL-26 is preferentially produced by human T_H17 cells and that this cytokine has both alarmin and direct antimicrobial functions.

Follicular helper T cells (T_FH 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 T_FH differentiation.

Follicular helper T cells (T_FH 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 T_FH differentiation by enhancing Bcl6 expression while suppressing that of Prdm1.