New Insights Into “T Helper Cells” Could Guide Future Multiple Sclerosis Therapies

A recent study entitled “STAT5 programs a distinct subset of GM-CSF-producing T helper cells that is essential for autoimmune neuroinflammation” describes a new subset of T helper immune cells – TH-GM – that express a particular cytokine profile with implications in therapeutics for multiple sclerosis. The study was published in the journal CellResearch.

Multiple sclerosis (MS) is a chronic autoimmune disease, characterized by the patient’s own immune system attacking its central nervous system, specifically a component of nerve fibers called myelin, which eventually leads to impairment and paralysis. Currently without any cure, MS affects more than 2.3 million people in the world, and while there are FDA-approved therapies for treating the disease, there are still serious unmet medical needs for MS patients.

In this study, the team of researchers led by Professor Xin-Yuan Fu, Senior Principal Investigator from CSI Singapore and Professor at the Department of Biochemistry at the NUS Yong Loo Lin School of Medicine, discovered a new subset of T helper immune cells — designated as TH-GM – with a key role in the pathogenesis of neuronal inflammatory diseases. The authors used mice with experimental autoimmune encephalomyelitis (EAE), the mouse model for human MS most commonly used, and found that STAT5, a member of the STAT protein family (STAT proteins regulate several pathways in the cell, including cell growth, survival and differentiation) regulates TH-GM in becoming auto reactive, leading to neuro inflammation.

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The authors discovered that a cytokine, interleukin 7 (IL-7), mediated regulation of STAT5 and this signaling axis – IL7-STAT5 – was a key pathway to the development of neuroinflammation. Specifically, the team performed in vitro studies and observed that the IL-7-STAT5 signaling axis induced the production of granulocyte-macrophage colony-stimulating factor (GM-CSF), a factor secreted by auto reactive T cells and previously suggested to sustain neuroinflammation.

Thus, the new subset of T cells regulated by IL7-STAT5 and that produce GM-CSF – TH-GM – represents a new cell subset with a distinct profile capable of inducing and sustaining neuroinflammation in autoimmune neuroinflammation diseases, including multiple sclerosis.