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Complement provides costimulatory signals to T cells. Medof and colleagues demonstrate that an absence of complement signaling in naive T cells generates an autoinductive loop to drive induced regulatory T cells.
Immune responses can cause immunopathology. Yarovinsky and colleagues show that IFN-γ induced by T cell–intrinsic TLR signaling in CD4+ TH1 cells during Toxoplasma gondii infection causes dysbiosis and loss of Paneth cells.
Interleukin 7 (IL-7) signaling is essential during early lymphocyte development. Patra and colleagues identify a distinct IL-7–kinase Jak3–dependent pathway that activates the transcription factor NFATc1 in DN1 thymocytes to promote their survival.
Why signaling via both the receptor for interleukin 7 (IL-7R) and the T cell antigen receptor (TCR) is required for T cell homeostasis has been unclear. Singer and colleagues show that engagement of the TCR interrupts IL-7R signals to prevent a mechanism of cytokine-induced cell death.
Follicular regulatory T cells control humoral immune responses, but how these cells are in turn controlled has been unclear. Sharpe and colleagues demonstrate that signaling via PD-1 regulates number and function of these cells.
The intracellular sensor DDX41 is important for generating innate responses to DNA viruses. Liu et al. demonstrate that the ubiquitin ligase TRIM21 degrades and thereby regulates DDX41-dependent responses.
Gaus and colleagues show that the conformational states of the tyrosine kinase Lck intrinsically control its distribution and clustering at the plasma membrane.
Psoriasis is associated with heightened TH17 responses. Li and colleagues show that the IL-17R signaling adaptor Act1 requires the chaperone protein hsp90. Defective signaling leads to exuberant IL-22 production and enhanced disease.
ARIH2 is a RING-between-RING E3 ligase. Pellegrini and colleagues show that ARIH2 is needed to limit excessive NF-κB signaling in DCs. Loss of ARIH2 is associated with embryonic death due to excessive inflammatory responses.
The signals involved in coordinating the navigation of myeloid cells in tissues are incompletely understood. Massberg and colleagues show that NG2+ pericytes control the pattern and efficacy of interstitial leukocyte migration.
Chronic infections can result in harmful production of the proinflammatory cytokine IL-1 generated via the NLRP3 inflammasome. Sassetti et al. demonstrate that IL-1 activated by Mycobacteria results in nitrosylation and consequent regulation of the NLRP3 inflammasome.
Trex1 is a cytosolic exonuclease that limits sensing of intracellular DNA. Yan and colleagues show that Trex1 deficiency spontaneously heightens adaptor STING–dependent proinflammatory responses via a pathway involving regulation of lysosomal biogenesis.
Modulation of integrin activation can contribute to regulation of inflammation. Arase and colleagues demonstrate that PILRα, an ITIM-containing inhibitory receptor, negatively regulates integrin activation and neutrophil infiltration during inflammation.
Activation of type I interferon by c-di-GMP and c-di-AMP depends on the adaptor STING. Cheng and colleagues show that these bacterial secondary messengers are detected by the helicase DDX41, which forms a complex with STING.
NK cell licensing is governed by the interaction of Ly49 receptors with peptide-MHC complexes. Smyth and colleagues show that the nonclassical MHC class I molecule H2-M3 can also license NK cell functional development.
The Igh locus undergoes a precise order of gene rearrangement during V(D)J recombination. Sen and colleagues show the recruitment of the RAG recombinase is confined to DJH junctions by highly localized epigenetic modifications.
The receptors for IL-2 and IL-15 share many characteristics, but mice deficient in either receptor have very different phenotypes. Garcia and colleagues present the quaternary structure of the complex of IL-15 and its receptor, as well as insights into its unique signaling properties.
The linear ubiquitination complex (LUBAC) is poorly understood in humans. Casanova and colleagues identify natural mutations in a component of human LUBAC and use this to dissect its function in vivo and in vitro.
Noncanonical RelB–NF-κB2 heterodimers function in homeostatic signaling. Hoffmann and colleagues show that RelB-p50 complexes, regulated by IκB, exist in dendritic cells and contribute to inflammatory gene expression via canonical NF-κB pathway activation.
The complement receptor CD46 and the Notch-Jagged system are important for the differentiation of helper T cells. Kemper and colleagues demonstrate that Jagged1 is a physiological ligand for CD46 and is critical for the generation of T helper type 1 cells in humans.