0000000000866888
AUTHOR
Anna Ebering
Time to activin on pathogenic T cells
In multiple sclerosis (MS), Th17 cells are critical drivers of autoimmune central nervous system (CNS) inflammation and demyelination. Th17 cells exhibit functional heterogeneity fostering both pathogenic and nonpathogenic, tissue-protective functions. Still, the factors that control Th17 pathogenicity remain incompletely defined. Here, using experimental autoimmune encephalomyelitis, an established mouse MS model, we report that therapeutic administration of activin-A ameliorates disease severity and alleviates CNS immunopathology and demyelination, associated with decreased activation of Th17 cells. In fact, activin-A signaling through activin-like kinase-4 receptor represses pathogenic t…
Unraveling the T-B tangle in anti-CD20 multiple sclerosis therapy.
Significance Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. CD8+ T cells have been strongly implicated in MS pathogenesis, but it is unclear whether myelin is a CD8+ T cell autoantigenic target in MS. This study demonstrated that while myelin-specific CD8+ T cells are present at similar frequencies in untreated MS patients and healthy subjects, the proportion of memory and CD20-expressing myelin-specific CD8+ T cells was increased in MS patients, suggesting prior antigen encounter. This activated phenotype was reversible as the memory and CD20-expressing populations of certain myelin-specific CD8+ T cells were reduced following anti-CD20 trea…
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…