Inducible and naturally occurring regulatory T cells enhance lung allergic responses through divergent transcriptional pathways.
Inducible and naturally occurring regulatory T cells enhance lung allergic responses through divergent transcriptional pathways.
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DOI：
10.1016/j.jaci.2016.06.051
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发表时间：
2017-04
期刊：
影响因子：
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通讯作者：
Gelfand EW
中科院分区：
文献类型：
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作者：
Joetham A;Schedel M;O'Connor BP;Kim S;Takeda K;Abbott J;Gelfand EW
T regulatory cells attenuate development of asthma in wild-type (WT) mice with both naturally occurring (nTregs) and inducible T regulatory cells (iTregs) exhibiting suppressive activity. When transferred into CD8-deficient (CD8−/−) recipients, both cell types enhanced development of allergen-induced airway hyperresponsiveness (AHR). To determine if the pathways leading to enhancement of lung allergic responses by transferred nTregs and iTregs differed. nTregs (CD4+CD25+) were isolated from WT mice and iTregs were generated from WT CD4+CD25− T cells following activation in the presence of TGF-β and transferred into sensitized CD8−/− recipients prior to challenge. Development of AHR, cytokine levels, and airway inflammation were monitored. Transfer of nTregs enhanced lung allergic responses as did transfer of iTregs. While anti-IL-13 reduced nTreg-mediated enhancement, it was ineffective in iTreg-mediated enhancement; conversely, anti-IL-17 but not anti-IL-13 attenuated the enhancement by iTregs. Recovered iTregs from the lungs of CD8−/− recipients were capable of IL-17 production and expressed high levels of signature genes of the Th17 pathway, RORγt, and Il17, while reduced expression of the Treg key transcription factor Foxp3 was observed. In vitro, exogenous IL-6-induced IL-17 production in the iTregs and in vivo, conversion of transferred iTregs was dependent on recipient IL-6. iTregs similar to nTregs exhibit functional plasticity and can be converted from suppressor cells to pathogenic effector cells enhancing lung allergic responses, but these effects were mediated through different pathways.
