A recent PLoS One study indicates that the cross-talk between the brain microglia and T cells that follows a microglia’s activation via Toll-like receptors (TLRs) stimulation, results in a shift of the T cells’ profile towards a neurotoxic IL-17+ γδ T cells phenotype.
The CD4+ Th17 cells were thought to be the major source of IL-17, but we now know that CD8+ T cells, natural killer (NK) cells, and γδ T cells also produce this central pro-inflammatory cytokine. Nowadays, however, γδ T cells are considered the major source of IL-17.
In the PLoS One article, Katja Derkow and colleagues from the Charité University Hospital, Berlin, Germany, have studied the interactions between γδ T cells and microglia activated by TLRs in relation to neuronal damage.
The authors report that soluble factors, such as IL-1β and IL-23 released by TLR-stimulated microglia, the major immune cells of the brain, induce MyD88-dependent activation of γδ T cells. This was indicated by the up-regulation of CD69 and CD25 and by the release of large amounts of IL-17.
They found that the presence of IL-17+ γδ T cells but not naïve γδ T cells, and, importantly, cell-to-cell contact between neurons and T cells, is required for the expression of neurotoxic effects of IL-17+ γδ T cells, as they observed in vitro.
Previous research has indicated a ‘neurotoxic profile’ of IL-17+ γδ T cells in murine models of ischemia/reperfusion and Alzheimer´s disease.
The authors speculate that through the above mechanisms in pathophysiological or clinical settings the entry of γδ T cells into the brain may cause intracellular IL-17 production via contact with microglia, and this effect may not require TLR signaling.
These mechanisms may have important implications for certain neuroinflammatory disorders such as multiple sclerosis, stroke and/or Alzheimer´s disease.