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New Type of Treg Cells Combat Brain Atrophy

May 14, 2014 1:00:22 PM / by Maria

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[1]. 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.

FoxA1 expressing Treg cells potent candiate for treating multiple sclerosis Multiple sclerosis is an autoimmune disease where myelin sheet wrapped around the axon is destroyed due to chronic inflammation. FoxA1 expressing Treg cells prevent the brain inflammation in multiple sclerosis model. Image credit: IyashiSource.com

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 [2]. 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[3] 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.

HemaCare is a reliable provider of human lymphocytes including CD3+, CD4+, CD8+ and CD4+/CD25+ regulatory T Cells.

References:

[1.] Calabresi PA. Diagnosis and management of multiple sclerosis. Am Fam Physician. 2004;70:1935–1944.

[2.] Compston A, Coles A "Multiple sclerosis". Lancet 359 (9313): 1221–31 (April 2002). 

[3.] Lupien, M. et al. FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription. Cell 132, 958–970 (2008).

Topics: Gene Therapy, apoptosis, Autoimmune Disorders, Cell Therapy, Inflammation, leukocyte differential, Regulatory T Cells, white blood cells, Basic Research

Maria

Written by Maria

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