Recent progress in understanding the pathogenicity of multiple sclerosis (MS) has enabled us to develop new drug entities available in the clinic. However, we still have not succeeded in preventing conversion from relapsing–remitting MS to secondary progressive MS (SP‐MS), and in curing this intractable form of MS. Furthermore, diagnosis is usually retrospective, relying on gradual worsening of neurological signs/symptoms. This is due to the lack of understanding of the pathogenicity driving disease progression in MS and of reliable biomarkers reflecting the disease status. Two relevant components are involved in the brain pathology of SP‐MS: neurodegeneration and inflammation. Neurodegeneration can occur spontaneously in a neuron‐intrinsic manner under chronic inflammation, such as glutamate excitotoxicity, mitochondrial/oxidative injury with iron deposit in the brain and loss of trophic support. Meanwhile, inflammatory and/or immune cells stimulated after repeated relapses, including T cells, B cells, and myeloid cells of peripheral and central nervous system origin, could mediate the processes of neurodegeneration. Among them, a higher frequency of leptomeningeal follicle‐like structures observed in SP‐MS patients suggests that immune cells sheltered behind a blood–brain barrier are still active under smoldering central nervous system inflammation. Accordingly, our recent comparative analysis between MS and its animal model, experimental autoimmune encephalomyelitis, raises a new possibility that ectopic expression of eomesodermin in helper T cells constitutes a previously unappreciated subset of helper T cells with cytotoxic potential against neuronal cells. In the present review article, the mechanisms proposed in the pathogenesis of SP‐MS are summarized, and a new pathogenic mechanism for neurodegeneration mediated by unique cytotoxic helper T cells is proposed.
Clinical and Experimental Neuroimmunology – Wiley
Published: Jan 1, 2018
Keywords: ; ; ; ;
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera