Granzyme B Is Critical for T Cell Receptor-Induced Cell Death of Type 2 Helper T Cells
(Immunity 25, 237–247; August 2006)
Immunity
UV irradiation drives lineage-specific MITF-mediated transcription of PD-L1 to confer immune tolerance to UV-mutated melanocytes
UVR-damaged melanocytes evade immune attack despite harboring many mutations. Lo et al. show that MITF, a transcriptional regulator crucial to melanocyte identity, directly induces the immune checkpoint molecule PD-L1. This intrinsic tolerance program …
The cost of persistence: MEK and metabolic demand
The metabolic mechanisms linking chronic TCR stimulation to T cell exhaustion remain incompletely understood. Mitra and colleagues show that sustained MEK signaling drives the bioenergetic demands of chronic activation to promote terminal exhaustion, w…
Coordinated transcriptional networks program organelle expansion and metabolic flows for high endothelial morphology and function
High endothelial venules require specialized morphology and PNAd expression to support lymphocyte homing; however, the transcriptional mechanisms coordinating these defining features have remained unclear. Bi et al. identify XBP1-dependent and CREB3L2-…
Copy and paste: Humanizing IgH 155 kb at a time
Generating mice that express human antibodies is a lengthy and labor-intensive process. Knocking in human gene segments into mice has potential, but how large a gene segment can be knocked into a zygote? Nair et al. insert a 155-kb human VH locus direc…
Peripheral vision: Treg cell induction in the gut
Some regulatory T (Treg) cells differentiate at peripheral sites in response to antigens derived from innocuous sources. In this issue of Immunity, Chi et al. examine an extensive array of T cell receptors with specificity for self, microbial, or dieta…
Different lysosomal insults, one microglial fate
Genetic associations point to a connection between lysosomal function and neurodegeneration. In this issue of Immunity, Balak et al. and Tejwani et al. show that genetically distinct lysosomal insults converge on a shared MITF/TFE-driven epigenetic pro…
CCR7+ activated dendritic cells are essential for spontaneous and immunotherapy-driven anti-tumor immunity
Dendritic cells (DCs) can acquire distinct functional states. To examine how different DC states orchestrate anti-tumor immunity, Koufaki et al. develop mouse models to label and ablate CCR7+ DCs and find that this activation state is essential for tum…
Progranulin deficiency-induced lysosomal dysfunction drives maladaptive myeloid cell states through the MITF/TFE transcription factors
Mutations in proteins with roles in lysosomal function, including progranulin, are linked with neurodegenerative diseases. Tejwani, Heffner, et al. demonstrate that lysosomal dysfunction is sufficient to drive epigenetic, transcriptional, and functiona…
Lysosomal dysfunction drives a transcriptional and epigenetic signature found in disease-associated microglia in neurodegenerative diseases
Lysosomal dysfunction is associated with neurodegeneration. Balak et al. examine the cell-specific effects of lysosomal dysfunction in an MPS-IIIA (Sgsh−/−) model and find that microglia are disproportionately affected. Mechanistically, the MITF/TFE tr…