The STATe of the Neuron Leads to Synaptic Stripping
In a recent issue of Cell, Di Liberto et al. (2018) elucidate the mechanisms involved in synaptic stripping during viral infection. Infected neurons orchestrate their own synaptic loss downstream of IFNγ signaling, ultimately attracting phagocytic monocytes into the CNS through CCL2 production.
Glutamate Excitotoxicity in the Cerebellum Mediated by IL-1β
Multiple sclerosis (MS) is the prototypic inflammatory demyelinating disorder of the CNS. Symptoms of cerebellar dysfunction, such as tremors and ataxia, are relatively common in MS, but available treatment options are generally of limited value. Although many clinical manifestations of MS are
Upgrading from iMac to iMicro
In this issue of Immunity, Takata et al. (2017) describe a novel method to differentiate macrophages from iPSCs. These cells, which they call iMacs, are similar to yolk-sac-derived macrophages and are capable of undergoing terminal differentiation into tissue-resident-like macrophages in vitro and in vivo.
NF-κB inducing kinase (NIK) is an essential post-transcriptional regulator of T-cell activation affecting F-actin dynamics and TCR signaling
NF-κB inducing kinase (NIK) is the key protein of the non-canonical NF-κB pathway and is important for the development of lymph nodes and other secondary immune organs. We elucidated the specific role of NIK in T cells using T-cell specific NIK-deficient (NIKΔT) mice. Despite showing normal development of lymphoid organs, NIKΔT mice were resistant to induction of CNS autoimmunity. T cells from NIKΔT mice were deficient in late priming, failed to up-regulate T-bet and to transmigrate into the CNS. Proteomic analysis of activated NIK-/- T cells showed de-regulated expression of proteins involved in the formation of the immunological synapse: in particular, proteins involved in cytoskeleton dy…
Imiquimod-Induced Psoriasis in Mice Depends on the IL-17 Signaling of Keratinocytes
The pathology of psoriasis strongly depends on IL-17A. Monoclonal antibodies blocking either the cytokine or its receptor are among the most efficient treatments for psoriatic patients. Keratinocytes can be activated upon exposure to IL-17A and tumor necrosis factor-α and secrete secondary cytokines and chemokines in the inflamed skin. In psoriasis and its imiquimod-induced mouse model, a strong skin infiltration of neutrophils and inflammatory monocytes can be observed. However, to date, it is not clear how exactly those cellular populations are attracted to the skin and how they contribute to the pathogenesis of the disease. To define the crucial cell type responding to IL-17 and initiati…
Elevated NKG2D ligand expression in experimental autoimmune encephalomyelitis
T cells remain unclear. Expressing myelin-reactive T cell receptor (TCR) is not sufficient to make a T cell encephalitogenic. In fact, the frequencies of myelin-reactive T cells are comparable between MS patients and healthy individuals, but the ones in MS patients have activated/memory phenotypes. In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), myelin-specific T cells activated with antigen presenting cells (APCs) plus myelin peptide are encephalitogenic, whereas T cells activated with anti-CD3/CD28 antibodies are not. This suggests that APCs provide critical cytokines beyond T cell receptor activation and co-stimulation, contributing to encephalitogenicity. To …