Immunosuppressive properties of novel FoxA1 expressing Treg cells can be exploited for multiple sclerosis treatment
Autoimmune pathology of multiple sclerosis:
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by brain inflammation, which cause the irreversible axonal damage. Brain inflammation of MS arises when the nervous system is attacked by the body's own immune cells. MS can develop due to viral infection and/or genetic defects or environmental factors. As yet, the exact etiology of the disease is unfortunately unknown. However it is known that the activation and differentiation of CD4+ T cells into a Th1 phenotype are a crucial event in the initiation of this disease.
The brain inflammation fighter cells:
The chronic inflammation in the brain during MS is caused by functional defects of Treg cells, a type of lymphocyte that plays an important role in the peripheral tolerance . Recently, a newly recognized subset of lymphocytes expressing the gene FoxA1 have been found to be involved in the suppression of brain inflammation. FoxA1 is a critical protein for epigenetic reprogramming and cell-lineage commitment for this kind of Treg cells. Researchers at University of Copenhagen have found a new population of Treg cells named FoxA1+ Treg cells. These cells with ectopic expression of the FoxA1 gene are able to suppress MS.
Development of these FoxA1+ Treg cells occurs primarily in the CNS in response to autoimmune inflammation. FoxA1 bind to the Pdl1 promoter and induce the programmed cell death ligand 1 (Pd-l1) expression, which in turn suppress T-cells by induction of apoptosis. Cytokine interferon-β (IFN-β), and IFN-α/β receptor (Ifnar) signaling play a very crucial role in development of FoxA1+ Treg cells, as the frequency of FoxA1(+) Treg cells was reduced in mice lacking the cytokine receptors.
It was also noticed that individuals with relapsing-remitting multiple sclerosis who exhibit encouraging clinical outcomes to IFN-β treatment have more frequency of FoxA1+ Treg cells in the blood. These findings suggest that understanding the function of FoxA1+ Treg could lead to new therapies for MS.
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