Thursday, 11 August 2016

Distinct types of immune cell associate with different lesions

Gross CC, Schulte-Mecklenbeck A, Hanning U, Posevitz-Fejfár A, Korsukewitz C, Schwab N, Meuth SG, Wiendl H, Klotz L.Distinct pattern of lesion distribution in multiple sclerosis is associated with different circulating T-helper and helper-like innate lymphoid cell subsets. Mult Scler. 2016 Aug 1. pii: 1352458516662726. [Epub ahead of print]
BACKGROUND:Distinct lesion topography in relapsing-remitting multiple sclerosis (RRMS) might be due to different antigen presentation and/or trafficking routes of immune cells into the central nervous system (CNS).
OBJECTIVE:To investigate whether distinct lesion patterns in multiple sclerosis (MS) might be associated with a predominance of distinct circulating T-helper cell subset as well as their innate counterparts.
METHODS:Flow cytometric analysis of lymphocytes derived from the peripheral blood of patients with exclusively cerebral (n = 20) or predominantly spinal (n = 12) disease manifestation.
RESULTS:Patients with exclusively cerebral or preferential spinal lesion manifestation were associated with increased proportions of circulating granulocyte-macrophage colony-stimulating factor (GM-CSF) producing TH1 cells or interleukin (IL)-17-producing TH17 cells, respectively. In contrast, proportions of peripheral IL-17/IL-22-producing lymphoid tissue inducer (LTi), the innate counterpart of TH17 cells, were enhanced in RRMS patients with exclusively cerebral lesion topography.
CONCLUSIONS:Distinct T-helper and T-helper-like innate lymphoid cell (ILC) subsets are associated with different lesion topography in RRMS.

This study suggests that different T cell types can drive lesions in the brain or spinal cord. those targeting the brain produced GM-CSF (a cytokines that promotes neutrophils and macrophages and some dendritic cells) and the spinal cord cells produced IL-17. In animals it has been reported that cells that develop an atypical cerebellar disease associated with lots of neutrophils (a cell involved in the first line defence against infections) but Th17 and the GM-CSF has been implicated in spinal EAE. So we best wait until this is repeated, but the implication s that we can have differential effects. Immunologists are deparately trying to control Th17 cells but this study suggests that it may not be universally effective and so one wonders is this why blockade of Interleukin-17 to block TH17 was relatively rubbish at blocking lesions in the brain of people with MS. It only gave about a 50% inhibition (this got the EAEologists excited to prove that TH17 is the bees knees...then some one mentioned beta interferon can do a lot better than that..

3 comments:

  1. If this get to be reproduced in other studies so EBV can then lead to uncontrolled activation of monocytes and macrophages accordingly?
    What from what I understood then really this is possible could be connected over the spinal cord injuries, or not?

    I remembered it because the results presented by Prof. G Charcot 2 show that about 45% of those MSers study participants were derramendo EBV in their saliva during analysis ...

    http://cdn.intechopen.com/pdfs-wm/23462.pdf

    http://www.ncbi.nlm.nih.gov/pubmed/12960485

    http://www.nature.com/gene/journal/v13/n4/full/gene20123a.html

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  2. Does this imply a distinct set of spinal vs. cerebellar etiologies?

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    1. I had thought of that too, in different causes for the same MS, so I asked, for example, if EBV would be more or linked to brain injury or spinal cord. Same thing with such a deficiency of vitamin D and poor way of Cholesterol Synthesis resulted in more spinal cord injuries...

      But if this is confirmed it would be too early to determine what the different etiologies have as consequences, if more spinal cord injuries or more brain lesions. And to understand why a person had a different causal pathway of others, for example.

      Yesterday I was talking to a person who said he was negative for me EBV infections or Cytomegalovirus, never had vitamin D defciência, and it has a case of rheumatoid arthritis in the family, but JC positive. She has more spinal cord injuries...

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