Mechanisms of Mucosal Th17 Cell Induction By Segmented Filamentous Bacteria
Mechanisms of Mucosal Th17 Cell Induction By Segmented Filamentous Bacteria
批准号:
10475627
负责人:
Ivaylo Ivanov Ivanov
金额:
$58.29万
依托单位国家:
美国
项目类别:
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-04-15 至 2024-08-31
关键词:
Antigen PresentationAntigen Presentation PathwayAntigen-Presenting CellsAntigensApoptosisApoptoticAutomobile DrivingAwardBacteriaCD4 Positive T LymphocytesCell Differentiation processCellsChronicDendritic CellsDevelopmentEnvironmentEpithelial CellsFundingGenerationsGenesGenetic ModelsHomeostasisHumanImmuneImmune responseImmunologicsImmunologyInfectionInflammationInflammatoryInflammatory Bowel DiseasesIntestinesLamina PropriaLymphoid CellMicrobeMucous MembraneMusNaturePathogenicityPathway interactionsPeyer&aposs PatchesPhagocytosisProcessRegulatory T-LymphocyteReportingResearch DesignRoleT cell responseT-LymphocyteTestingTissuesadaptive immunitycellular targetingcommensal bacteriadesigneffector T cellgut bacteriagut microbiotainterestintestinal epitheliummacrophagemesenteric lymph nodemucosal microbiotanovelpathogenpathogenic bacteriapreservationpreventresident commensalsresponse
中文摘要
肠道常驻细菌如何参与适应性免疫尚不清楚。共生特异性 T 细胞很困难
在 LP 中进行检测,并且已经描述了多种机制来防止这种情况的发展
细胞处于稳态。这些包括管腔中的隔离和免疫学无知、重定向
共生特异性 T 细胞进入 Treg 区室,并通过 3 型先天负选择
淋巴样细胞(ILC3)。我们已经确定了一个共生宿主相互作用的例子,其中
分段丝状细菌 (SFB) 诱导抗原特异性非炎症 Th17 细胞反应。
因此,某些共生体确实会参与适应性免疫并产生效应 T 细胞,这些细胞
显然是非炎症性的。该过程涉及的机制尚不清楚,但
重大兴趣,因为它们可能有助于设计抑制效应 T 炎症潜力的策略
细胞,同时保留其效应功能。我们还表明,这个过程是通过一种独特的方式发生的
需要肠道巨噬细胞(Mfs)的抗原呈递途径。在此我们建议进行调查
肠道 Mfs 的机制作用以及诱导的 Th17 细胞的致病性。我们也
表明肠上皮细胞参与细菌和 Mfs 之间的串扰,并将
研究这种相互作用的新的潜在机制。我们将研究以下具体目标:
1)我们将鉴定呈递SFB抗原的先天免疫亚群; 2)我们将描述共同
肠上皮细胞、Mfs和树突状细胞在生成Th17细胞中的作用; 3)我们会
研究生成的 Th17 细胞的致病性并鉴定调节其能力的基因
引起炎症; 4)我们将检查是否有类似的抗原呈递途径参与
人类共生细菌诱导 Th17 细胞。
英文摘要
How resident gut bacteria engage adaptive immunity is not clear. Commensal specific T cells are difficult
to detect in the LP and multiple mechanisms have been described that prevent development of such
cells at steady state. These include sequestration in the lumen and immunological ignorance, re-direction
of commensal-specific T cells into the Treg compartment, and negative selection by type 3 innate
lymphoide cells (ILC3). We have identified an example of commensal-host interaction in which
segmented filamentous bacteria (SFB) induce an antigen-specific non-inflammatory Th17 cell response.
Therefore, certain commensals do engage adaptive immunity and generate effector T cells that are
apparently non-inflammatory. The mechanisms involved in this process are not known, but are of
significant interest, because they may help design strategies to curb inflammatory potential of effector T
cells, while preserving their effector function. We also showed that this process occurs through a unique
antigen-presentation pathway that requires intestinal macrophages (Mfs). Here we propose to investigate
the mechanistic role of intestinal Mfs as well as the pathogenicity of the induced Th17 cells. We also
show that intestinal epithelial cells are involved in the crosstalk between the bacteria and Mfs, and will
investigate a novel potential mechanism of this interaction. We will investigate the following specific aims:
1) we will identify the innate immune subset presenting SFB antigens; 2) we will characterize the co-
operative role of intestinal epithelial cells, Mfs and dendritic cells in generating Th17 cells; 3) we will
investigate the pathogenicity of the generated Th17 cells and identify genes that regulate their ability to
cause inflammation; 4) we will examine whether a similar antigen-presentation pathway is involved in
induction of Th17 cells by human commensal bacteria.
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DOI:
10.1038/icb.2012.80
发表时间:
2013-03
期刊:
IMMUNOLOGY AND CELL BIOLOGY
影响因子:
4
作者:
[Goto, Yoshiyuki, Ivanov, Ivaylo I.]
通讯作者:
Ivanov, Ivaylo I.
Intestinal microbiota-specific Th17 cells possess regulatory properties and suppress effector T cells via c-MAF and IL-10.
肠道微生物群特异性 Th17 细胞具有调节特性,并通过 c-MAF 和 IL-10 抑制效应 T 细胞。
DOI:
10.1016/j.immuni.2023.11.003
发表时间:
2023
期刊:
Immunity
影响因子:
32.4
作者:
[Brockmann,Leonie, Tran,Alexander, Huang,Yiming, Edwards,Madeline, Ronda,Carlotta, Wang,HarrisH, Ivanov,IvayloI]
通讯作者:
Ivanov,IvayloI
DOI:
10.1038/ncomms2718
发表时间:
2013
期刊:
Nature communications
影响因子:
16.6
作者:
[]
通讯作者:
DOI:
10.1016/j.jim.2015.03.020
发表时间:
2015-06
期刊:
Journal of immunological methods
影响因子:
2.2
作者:
[Farkas AM, Panea C, Goto Y, Nakato G, Galan-Diez M, Narushima S, Honda K, Ivanov II]
通讯作者:
Ivanov II
DOI:
10.1016/j.immuni.2014.03.005
发表时间:
2014-04-17
期刊:
IMMUNITY
影响因子:
32.4
作者:
[Goto, Yoshiyuki, Panea, Casandra, Nakato, Gaku, Cebula, Anna, Lee, Carolyn, Diez, Marta Galan, Laufer, Terri M., Ignatowicz, Leszek, Ivanov, Ivaylo I.]
通讯作者:
Ivanov, Ivaylo I.
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