Nat Med. 2018. doi: 10.1038/s41591-018-0236-y. [Epub ahead of print].
Multiple sclerosis (MS) is characterized by an immune system attack targeting myelin, which is produced by oligodendrocytes (OLs). We performed single-cell transcriptomic analysis of OL lineage cells from the spinal cord of mice induced with experimental autoimmune encephalomyelitis (EAE), which mimics several aspects of MS.
We found unique OLs and OL precursor cells (OPCs) in EAE and uncovered several genes specifically alternatively spliced in these cells. Surprisingly, EAE-specific OL lineage populations expressed genes involved in antigen processing and presentation via major histocompatibility complex class I and II (MHC-I and -II), and in immunoprotection, suggesting alternative functions of these cells in a disease context.
Importantly, we found that disease-specific oligodendroglia are also present in human MS brains and that a substantial number of genes known to be susceptibility genes for MS, so far mainly associated with immune cells, are expressed in the OL lineage cells.
Finally, we demonstrate that OPCs can phagocytose and that MHC-II-expressing OPCs can activate memory and effector CD4-positive T cells.
Our results suggest that OLs and OPCs are not passive targets but instead active immunomodulators in MS. The disease-specific OL lineage cells, for which we identify several biomarkers, may represent novel direct targets for immunomodulatory therapeutic approaches in MS.
I think it is not really O1 and O2, but O macrophage as the oligodendrocytes are reported to have the functions of antigen presenting cells. This is all well and dandy but….
The first question we should ask is….why?
The immune system has evolved over many years to have specific functions. In the 1980s we went over this, over and over again and it was found that a Wellington Boot that expressed MHC class II could present antigens to T cells. OK I’m being a bit flippant, but you know where I am coming from.
There was study upon study. Ask MD2. He showed you could get endothelium to express MHC antigens. His work was repeated about 15 years later…without being cited…but the result was “So what.”
I would say that oligodendrocytes are not specialized for this activity and when people looked with electronmicropscopy it was indicated that the cells expresssing the MHC class II were not astrocytes, nerves, oligodendrocytes, endothelial cells in most cases but microglial-like cells.
The Brain is full of microglial cells capable of engulfing stuff and presenting antigens. Why do we need antigen presenting oligodendrocytes? Will someone come along in twenty years and say hey Microglia make myelin? If they do will we take notice?
In this study they look at single cells and the message they make.
In this study they look at the gene products and suggest that oligodendrocytes make MHC class I and MHC class II and so T cell MS is back on…and CD8 and CD4 could be doing the killing.
Phew say a million and one T cell biologists, their work is back in the spot light again.
Will it be repeated as surely it has to be….A quick look on http://www.brainseq2 and you find it. e.g HLA-A and HLA-DRA
But, we have been there before 🙁