TLRs-Activated Microglia Polarizes γδ T Cells towards a Neurotoxic IL-17+ γδ T Cell Phenotype: Implications for Multiple Sclerosis, Stroke and Alzheimer´s Disease
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.
After the discovery of T helper (Th)17 cells in 2005, their main product, IL-17, has rapidly emerged as a key player in the pathogenesis of several autoimmune/inflammatory diseases. This includes rheumatoid arthritis, psoriasis, inflammatory bowel disease, systemic lupus erythematosus and multiple sclerosis (MS).
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.
γδ T cells represent a distinct population of T cells, approximately 1–5% of the total lymphocytes, and appear to be ‘specialized’ in a rapid ‘innate-like’ immune response and a first line of defense from various infections via their expression of TLRs. TLRs are protein receptors that respond and recognize highly conserved components from viruses, bacteria, fungi, and parasites.
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.
Source: PLoS One. 2015; 10(8):e0135898. doi: 10.1371/journal.pone.0135898. eCollection 2015.
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