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Table 2: Main immune mediators of oligodendrogenesis in the adult brain
Signal Cells Function
CXCL10 Produced by astrocytes [94] Promotes the migration of microglia and macrophages to the
demyelinated areas to phagocytose the damaged myelin sheaths [94]
CXCL12 Produced by microglia and astrocytes [96] Mobilizes and stimulates OPC differentiation into
Binds to CXCR4 on the surface of OPCs [97] oligodendrocytes [96]
CXCL1 Produced by astrocytes [98] Prevents apoptosis of oligodendrocytes in demyelinated white
Binds to CXCR2 on the surface of proliferating matter areas [99]
OPCs and reactive astrocytes [98]
CXCR2 Enhances OPC differentiation [100]
blockade Reduces the extent of microglia activation and the number of
infiltrating inflammatory cells [100]
CNTF‑IL‑6 Produced by astrocytes [101] Protects axons and OPCs [102,103]
family Controls SVZ-derived progenitor cells and OPC mobilization and
migration toward demyelinated areas [104]
Promotes oligodendrocyte maturation [93]
IL-1β Mainly produced by microglia, macrophages, Promotes OPC protection and differentiation by stimulating
astrocytes, and oligodendrocytes [105] microglia, macrophages, and astrocytes to produce
growth‑promoting factors, such as IGF‑1, and also TNF‑α and nitric
oxide [106-108]
IL-4 Produced by T cell [109] Promotes microglia activation which produces IGF‑1 [109]
TNF‑α Produced by microglia and astrocytes [110] Promotes proliferation and accumulation of OPCs [111]
Binds to TNFR2 present on the surface of OPCs [111]
TNF‑α depletion Decreases proliferation of NG2+immature oligodendrocytes [111]
OPC: oligodendrocyte precursor cell; SVZ: subventricular zone; IGF‑1: insulin‑like growth factor‑1; TNF‑α: tumor necrosis factor‑α; NG2: neuron‑glial antigen 2;
IL‑1β: interleukin‑1beta; IL‑4: interleukin‑4; TNFR2: tumor necrosis factor receptor 2; CNTF: ciliary neurotrophic factor; IL‑6: interleukin‑6

There are still contradictory actions of immune
mediators that need to be clarified. The use of limited
models of demyelination can be a cause for some of
those differences. Thus, it is necessary to develop
combined models that will help us to better understand
the mechanisms of demyelination and remyelination.
How cell immune mediators can be either beneficial or
detrimental to the remyelination process and how these
responses can change with aging are key questions to
successfully develop remyelinating or neuroprotective
therapeutic strategies.
Figure 4: Schematic representation of modulators of oligodendrogenesis in the
adult brain. Wnt and Notch positively regulate neural stem cells self-renewal.
Fibroblast growth factor‑2, laminin, Ascl1, Nkx6.1/6.2, Sox 8/9, miRNA‑7a CONCLUSION
and histone methylation positively modulate oligodendrocyte fate. Histone
acetylation inhibits while epidermal growth factor and platelet-derived growth In the CNS, myelin is produced and maintained by
factor receptor α promotes oligodendrocyte precursor cell differentiation. Sirt1
and bone morphogenic proteins block while Insulin-like growth factor-1 stimulates oligodendrocytes. Therefore, new treatments to overcome
oligodendrocyte differentiation demyelinating disorders could be primed by targeting
this type of cell. In fact, in a demyelinating disorder,
role in the repair process, such as regulating OPC parenchymal OPCs spontaneously remyelinate newly
proliferation, migration, and differentiation into new nude axons in damaged areas. Moreover, NSCs can be a
myelinating oligodendrocytes [Table 2]. In other words, source of new oligodendrocytes for use in regenerative
the inflammatory response seems not merely a cause for medicine concerning myelin pathologies. In this
demyelination but rather a prerequisite for a successful review, we have highlighted some of the key players of
remyelination. oligodendrogenesis and that may be used in the future for
therapies concerning demyelinating disorders [Figure 4].
With the progression of the demyelinating disease,
or even with ageing, there is an impairment of Financial support and sponsorship
the remyelination process due to a decrease of Sara Xapelli (SFRH/BPD/76642/2011) and Filipa
pro‑oligodendrogenic signals and an increase of F. Ribeiro (SFRH/BD/74662/2010) were funded by
anti‑oligodendrogenic signals from immune cells Fundação para a Ciência e a Tecnologia (FCT), Portugal.
that compromises oligodendrocyte maturation and
myelination, leading to high inflammation and cell Conflicts of interest
death. [42,106,112] There are no conflicts of interest.

270 Neuroimmunol Neuroinflammation | Volume 2 | Issue 4 | October 15, 2015 Neuroimmunol Neuroinflammation | Volume 2 | Issue 4 | October 15, 2015 271