感染症と治療のジャーナル オープンアクセス

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Involvement of Th17/Treg cells and cytokines in Obstructive Sleep Apnea

Marcella Reale 

Obstructive sleep apnea (OSA) has pathophysiologic characteristics that are known to negatively impact immune function. The repetitive cycles of hypoxia/reoxygenation and connected arousals activate inflammatory pathways, and the cardiovascular dysfunction. Consequence of hypoxia/reoxygenation phenomena is the activation of NF-kB and increased production of inflammatory cytokines, and the differentiation of Th17 cells. The balance between Foxp3+ Treg and Th17 cells was determined by IL-6 that modulates the TGFβ-induced generation of Foxp3+ Treg and drive Th17 cell differentiation. The balance between TGFβ, an immunosuppressive cytokine, and IL-6, a pro-inflammatory cytokine, might influence the final outcome in the differentiation process of different effector T cell subsets. Recently, several genes underlying inflammatory pathways has been demonstrated to be differently expressed in peripheral blood leukocytes of patients with OSA, suggesting that OSA activates widespread pro-inflammatory networks increasing the levels of inflammatory mediators that promote development of medical comorbidities. Our results suggested that in the micro-environment of OSA patients, the increase of pro- inflammatory IL-6 and the reduction of TGFβ potentially promote the Th17/Treg imbalance. The shift of IL-17/TGFβ balance toward IL-17 might enhance the accumulation of inflammatory mediators, and finally generate a proinflammatory loop to amplify proinflammatory environment that in moderate-severe OSA patients shift the balance between Th1/Treg cells toward Th1 cells. Although IL-17 has no significant higher circulating levels in our OSA patients, taking into account its significantly high expression levels, we cannot exclude a role for IL-17 in OSA-related inflammation. Thus, IL-17 in conjunction with reduced TGFβ, modulate the development of Treg cells, causing a Th17/Treg imbalance. An intriguing hypothesis is that in OSA the balance between Th1 cells and Treg cells as well balance between M1 e M2 could be shifted respectively by up- regulation of IL-6 and down-regulation of TGFβ toward an inflammatory Th1 and M1 cell phenotype.