February 2016 | Volume 213, No. 2
Brief Definitive Reports
- A novel human autoimmune syndrome caused by combined hypomorphic and activating mutations in ZAP-70
Chan et al. describe a combination of alleles with hypomorphic and activating mutations in the T cell signaling molecule ZAP-70 in a patient with autoimmunity.
- Btn2a2, a T cell immunomodulatory molecule coregulated with MHC class II genes
Butyrophilins are proteins secreted during lactation and thought to influence immune function. Sarter et al. generated butyrophilin-2a2–deficient mice to show enhanced effector T cell responses, antitumor responses, and exacerbated EAE due to the impaired APC modulation of T cell immunity.
- RAG-mediated DNA double-strand breaks activate a cell type–specific checkpoint to inhibit pre–B cell receptor signals
B-lineage cells reconcile the competing needs of proliferation and genome stability.
- Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide
Madera et al. show that NK cells unable to receive type I IFN signals during MCMV infection have defective expansion and memory cell formation, possessing increased susceptibility to apoptosis due to NK cell–mediated fratricide.
- miR-23∼27∼24 clusters control effector T cell differentiation and function
The miR-23∼27∼24 clusters control differentiation of effector T cells. In particular, miR-24 targets IL-4 and miR-27 targets GATA3, thus collaborating in the control of Th2 immunity.
- IL-1–induced Bhlhe40 identifies pathogenic T helper cells in a model of autoimmune neuroinflammation
Lin et al. show that Bhlhe40 expression identifies encephalitogenic CD4+ T helper cells and define a pertussis toxin–IL-1–Bhlhe40 pathway active in experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis.
- Ptch2 loss drives myeloproliferation and myeloproliferative neoplasm progression
Klein et al. show that Ptch2 loss in either the niche or in hematopoietic cells drives myeloproliferation and accelerates JAK2V617F-driven pathogenesis, causing transformation of nonlethal chronic MPNs into aggressive lethal leukemias.