Interferon gamma-Producing Th17 Subsets: Major Contributors to "Th1" Diseases
Interferon gamma-Producing Th17 Subsets: Major Contributors to "Th1" Diseases
批准号:
9182439
负责人:
LAURA L KOTH
金额:
$7.93万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-06-13 至 2018-05-31
关键词:
Activities of Daily LivingAdrenal Cortex HormonesAffectAsthmaAttentionBioinformaticsBiological AssayBiologyBlood specimenBronchoalveolar LavageBronchoscopyCCR6 geneCD4 Positive T LymphocytesCXCR3 geneCellsCrohn&aposs diseaseCytometryDataDefectDiseaseEnzymesExhibitsFlow CytometryFrequenciesGenesGoalsGranulomaHumanImmuneImmunophenotypingInflammationInflammatoryInterferon Type IIInterleukin-12Interleukin-17Interleukin-4KnowledgeLinkLiteratureLungMeasurementMeasuresMethodsOrganOxidasesPathogenicityPhenotypePilot ProjectsPopulationProcessProductionProgressive DiseaseProliferatingProteinsPublicationsPublishingPulmonary Function Test/Forced Expiratory Volume 1Pulmonary SarcoidosisResearchResistanceRespiratory physiologyRoleSarcoidosisSeverity of illnessSignal PathwayStagingSteroidsT-LymphocyteTechnologyTestingTh1 CellsTranscriptUp-Regulationabstractingasthmaticbasebiobankcell typecohortcytokinedisorder controlinsightinventionnovel strategiesresponsetraittrend
中文摘要
摘要:我们最近在两个独立的队列中发现了最普遍的免疫细胞
英文摘要
Abstract: We have recently discovered in two separate cohorts that the most prevalent immune cells
producing interferonγ (IFNγ) in pulmonary sarcoidosis lung lavage are not Th1 cells but another cell which has
been identified as a highly pathogenic subset of Th17 cells, called Th17.1, due to their enhanced ability to
produce IFNγ among other functions. These findings challenge the Th1 paradigm that has held sway in
sarcoidosis since the invention of research bronchoscopy. But more importantly, our findings have the ability to
shift the research focus to these Th17.1 cells, about which we know little of their pathogenic traits and
functional differences compared to Th17 cells in sarcoidosis. The literature suggests that Th17.1 cells appear
to be derived from classically polarized Th17 cells which are highly “plastic” and can be stimulated to turn on
Th1-related signaling pathways by proinflammatory cytokines such as IL-12. Th17.1 cells in sarcoidosis do not
appear to share proliferative defects as documented for Th17 cells. We also know from Crohn's disease that
Th17.1 cells exhibit corticosteroid resistance. In our data, we found a trend in correlation between worsening
lung function (FEV1 % predicted) with increasing percentage of Th17.1 cells. This suggests that Th17.1 cells in
sarcoidosis may contribute to disease severity but cellular mechanisms have not been explored. In addition,
another distinct subset of Th17 linage cells have been identified in published studies and are called “Th17-
derived Th1 cells”. These cells are thought to be even more polarized towards a Th1 phenotype than Th17.1
cells due to their loss of IL-17A secretion and marked production of IFNγ. Thus, our finding of high frequencies
of Th17.1 cells in sarcoidosis raises the question of whether the cells we have long termed “Th1” in sarcoidosis
could actually instead belong to this Th17-derived Th1 subset. Therefore, we hypothesize that Th17 cells are
plastic and their biologic phenotype exists in a continuum from Th17→Th17.1→Th17-derived Th1 cells in the
milieu of polarizing cytokines IL-12 and IFNγ found in sarcoidosis. These polarized Th17 cells have pathogenic
potential to promote sarcoidal inflammation and cause progressive disease. Thus, we propose to interrogate
the proliferative capacity and related functions of Th17 vs Th17.1 cells in sarcoidosis compared healthy
controls and asthmatics. We will also use flow cytometry and CyTOF methods to measure the range of Th17
subsets and their ability to resist corticosteroid effects.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
The Impact of Environmental Exposures on Sarcoidosis Incidence and Mortality
-
批准号:10834640
-
项目类别:
-
资助金额:$10.16万
-
财政年份:2023
-
负责人:LAURA L KOTH
-
依托单位:
Development of Clinical Prediction Models for Pulmonary Outcomes in Sarcoidosis
-
批准号:10591517
-
项目类别:
-
资助金额:$105.95万
-
财政年份:2022
-
负责人:LAURA L KOTH
-
依托单位:
Development of Clinical Prediction Models for Pulmonary Outcomes in Sarcoidosis
-
批准号:10446452
-
项目类别:
-
资助金额:$115.38万
-
财政年份:2022
-
负责人:LAURA L KOTH
-
依托单位:
Immunophenotyping and Lymphocyte Effector Functions in Sarcoidosis
-
批准号:8128048
-
项目类别:
-
资助金额:$38.63万
-
财政年份:2010
-
负责人:LAURA L KOTH
-
依托单位:
Effector function of natural killer T (NKT) cells in sarcoidosis
-
批准号:7799789
-
项目类别:
-
资助金额:$7.65万
-
财政年份:2009
-
负责人:LAURA L KOTH
-
依托单位:
Effector function of natural killer T (NKT) cells in sarcoidosis
-
批准号:7846512
-
项目类别:
-
资助金额:$2.32万
-
财政年份:2009
-
负责人:LAURA L KOTH
-
依托单位:
Effector function of natural killer T (NKT) cells in sarcoidosis
-
批准号:7660211
-
项目类别:
-
资助金额:$7.73万
-
财政年份:2009
-
负责人:LAURA L KOTH
-
依托单位:
MCP-1 and TGFb in Macrophage Activation and Emphysema
-
批准号:6598747
-
项目类别:
-
资助金额:$12.18万
-
财政年份:2003
-
负责人:LAURA L KOTH
-
依托单位:
MCP-1 and TGFb in Macrophage Activation and Emphysema
-
批准号:6890463
-
项目类别:
-
资助金额:$12.18万
-
财政年份:2003
-
负责人:LAURA L KOTH
-
依托单位:
MCP-1 and TGFb in Macrophage Activation and Emphysema
-
批准号:7055304
-
项目类别:
-
资助金额:$12.18万
-
财政年份:2003
-
负责人:LAURA L KOTH
-
依托单位:
MCP-1 and TGFb in Macrophage Activation and Emphysema
-
批准号:6744788
-
项目类别:
-
资助金额:$12.18万
-
财政年份:2003
-
负责人:LAURA L KOTH
-
依托单位:
MCP-1 and TGFb in Macrophage Activation and Emphysema
-
批准号:7219428
-
项目类别:
-
资助金额:$12.18万
-
财政年份:2003
-
负责人:LAURA L KOTH
-
依托单位: