A study by Wanqiang Sheng and colleagues from the National University of Singapore, published in Cell Research identifies a new subset of T helper (Th) cells that may play a key role in autoimmune neuroinflammatory conditions such as multiple sclerosis.
Recent evidence indicates that granulocyte-macrophage colony-stimulating factor (GM-CSF) is a major encephalitogenic factor contributing to neuroinflammation and experimental autoimmune encephalomyelitis, the animal model of human demyelinating diseases, including multiple sclerosis (L. Codarri et al., Nature Immunology 2011, 12:560; M. El-Behi et al., Nature Immunology 2011, 12:568). A new study also suggests a pathogenic role for GM-CSF+ T cells in the inflamed brain of multiple sclerosis patients (R. Noster et al., Sci Transl Med, 2014, 241:241ra80).
Now, the research group from Singapore found that interleukin (IL)-7, signaling through STAT5, induces the development of a Th subset of cells (Th-GM) that predominantly produce GM-CSF and IL-3.
According to the authors (and cf. recent work indicating that anti-IL-23 receptor antibodies failed in treating multiple sclerosis), the function of IL-23 in multiple sclerosis is most likely compensated by other factors. Thus, in their study they found that Th-GM cells produced greater amounts of GM-CSF than Th1 or Th17 cells, suggesting that Th-GM cells are the major source of GM-CSF in T cell-mediated neuronal inflammation. This subset of Th cells was essential for the pathogenesis of experimental autoimmune encephalomyelitis, but not in experimental colitis.
The authors suggest that GM-CSF-producing CD4+ T cells regulated by IL-7-STAT5 signaling axis represent a new Th subset with a distinct differentiation program and cytokine production profile.