In damaged brains, two microglial phenotypes have been well-characterized. There is the classical activation of microglia (M1) and the alternative activation (M2).
The regulation of microglia activation has been focused to the repair of injured brains.
Numerous studies suggested that alternative activation of microglia supports brain function, whereas the classical microglia activation induces proinflammatory signals and hinder repair.
2. Tumor-associated immunosuppressive macrophages
 |
| Nakagawa and Chiba, 2014 Pharmaceuticals |
It is well known that activated M1 microglia can switch to M2 phenotype by various mediators, or factor.
Why have only one cell with dual or various function in neuroinflammation?
M1 and M2 microglia polarization is similar to Tumor-associated immunosuppressive macrophages.
Basically, Tumor cells produce suppressive factors that directly act on regulatory T (TReg) cells or license myeloid-derived suppressor cells, tumor-associated macrophages and dendritic cells to expand TReg cells.
Why have only one cell with dual or various function in neuroinflammation?
M1 and M2 microglia polarization is similar to Tumor-associated immunosuppressive macrophages.
Basically, Tumor cells produce suppressive factors that directly act on regulatory T (TReg) cells or license myeloid-derived suppressor cells, tumor-associated macrophages and dendritic cells to expand TReg cells.
 |
| Colombo and Piconese, 2007 Nat Review Cancer |
In immunology, DC cells can expand Treg cell, but in the brain, there are no DC cells and other APCs, because brain is immune-privileged organ.
3. Immune previlege of brain
Definition: - Product of multiple anatomical, physiological and immunoregulatory processes, leading to
1. Foreign molecules will not be recognized from the immune system in the CNS
(~see nothing)
2. Change/removal of inflammation to a less destructive response (inflammation)
(~hear nothing)
3. Inflammation is not spread outside the CNS
(~say nothing)
4. The concept of M2-like stem cells was raised
Several anatomical, physiological and immunoregulatory mechanisms leading to inhibition of autoimmune inflammation:
- Anti-inflammatory (TGFb)
- Propapoptotic (for invader)
- Brain specific antigens barely reach the cervical lymph node
- Presence of the blood-brain barrier
- Low expression of MHC molecules
- Absence of dendritic cells and other professional APCs etc.
The answer to why only one cell, specially microglia have a diverse function to detrimental or beneficial effect to neuron is:
- Propapoptotic (for invader)
- Brain specific antigens barely reach the cervical lymph node
- Presence of the blood-brain barrier
- Low expression of MHC molecules
- Absence of dendritic cells and other professional APCs etc.
The answer to why only one cell, specially microglia have a diverse function to detrimental or beneficial effect to neuron is:
Firstly, Microglia/macrophages are highly plastic cells that can assume diverse phenotypes and engage different functional programs in response to specific microenvironmental signals
Secondly, it is due to microglia and macrophages have different ontogeny in development.
Therefore, the concept of M2-like stem cells was raised!!
Secondly, it is due to microglia and macrophages have different ontogeny in development.
Therefore, the concept of M2-like stem cells was raised!!