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Amphiregulin-Immunometabolism axis in oral immunity and inflammation during HIV infection

HIV感染期间口腔免疫和炎症中的双调蛋白-免疫代谢轴

基本信息

批准号：
10621958
负责人：
Pushpa Pandiyan
金额：
$ 53.51万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-01 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10621958
关键词：
Address Age Aging Amphiregulin Attenuated Bioinformatics Biopsy CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes Cell physiology Cells Clinical Clinical Immunology Data Dentistry Diagnosis FOXP3 gene Feedback Flow Cytometry Functional disorder Fungal DNA Gingiva Goals HIV HIV Infections Health Human Human Papillomavirus Hypoxia IRAK1 gene Immune Immune System Diseases Immune response Immune system In Vitro Individual Inflammasome Inflammation Inflammatory Interleukin-1 beta Intervention Ligands Ligation Link Literature Lymphoid Lymphoid Tissue Measurement Mediating Metabolic Mouth Diseases Mucosal Immunity Mucous Membrane Oral Oral Medicine Oral cavity Oral mucous membrane structure Organoids Pathway interactions Persons Proteins Proto-Oncogene Proteins c-akt Regulatory T-Lymphocyte Residual state Role SYK gene Saliva Salivary Signal Pathway Signal Transduction Site Smoking T-Lymphocyte TLR2 gene Testing Tissues Tonsil Up-Regulation Viral reservoir Work antiretroviral therapy beta diversity clinical practice co-infection comorbidity dectin 1 dysbiosis gut microbiome immune health immunoregulation in vivo inflammatory milieu insight metabolome microbiome microbiome analysis microbiome composition microbiota mortality multidisciplinary novel oral fungal oral immunity oral microbiome oral tissue programmed cell death protein 1 programs receptor single-cell RNA sequencing systemic inflammatory response transcriptomics

项目摘要

ABSTRACT Systemic inﬂammation and mortality in people living with HIV (PLWH) are associated with mucosal immune dysfunction and persistent viral reservoirs in the mucosa and lymphoid tissues. In the previous project period, we have demonstrated the role of CD4+ FOXP3+regulatory T cells (Treg) dysregulation in contributing to aging- and HIV-associated oral inﬂammation. The dysfunctional Tregs that we uncovered in the oral mucosa of PLWH mimic tissue-resident CD4+ T cells expressing high levels of PD-1 and amphiregulin (AREG). These cells correlate with CD38+HLADR+ CD4+T cell hyperactivation and dysfunction, toll-like receptor 2 (TLR-2), and inﬂammasome/IL-1β signaling in vivo, and require IL-1β/AKT pathways for their expansion in the context of HIV infection. Here we propose to address the role of oral fungal dysbiosis in establishing the inﬂammatory environment and triggering oral immune cells to become dysfunctional. Building on our more recent results from salivary metabolome analysis in PLWH, we will examine the underlying pathways at the interface of dectin-1, AREG, inﬂammasome, and immunometabolism signaling pathways in three well-connected aims. Thus, our proposal will reveal new directions to manage oral immune-dysfunction and thereby systemic inﬂammation, and alter current clinical practice.

摘要 HIV感染者（PLWH）的系统性炎症和死亡率与粘膜炎症相关。免疫功能障碍和粘膜和淋巴组织中的持续病毒储库。上一在项目期间，我们已经证明了CD 4 + FOXP 3+调节性T细胞（Treg）失调在导致衰老和HIV相关的口腔炎症。我们发现的功能失调的甲状腺 PLWH的口腔粘膜模拟表达高水平PD-1和双调蛋白的组织驻留CD 4 + T细胞（AREG）。这些细胞与CD 38 +HLADR+ CD 4 +T细胞过度活化和功能障碍相关，Toll样受体2（TLR-2），并在体内的巨噬细胞/IL-1β信号传导中，并且需要IL-1β/AKT通路来实现其功能。在艾滋病毒感染的背景下扩大。在这里，我们建议解决的作用，口腔真菌生态失调，建立炎症环境并触发口腔免疫细胞功能失调。建筑根据我们最近对PLWH唾液代谢组学分析的结果，我们将研究潜在的免疫代谢信号通路，三个紧密相连的目标。因此，我们的建议将揭示新的方向，以管理口腔免疫功能障碍从而全身炎症，并改变当前的临床实践。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Inflammation, Immune Senescence, and Dysregulated Immune Regulation in the Elderly.

DOI：
10.3389/fragi.2022.840827
发表时间：
2022
期刊：
FRONTIERS IN AGING
影响因子：
0
作者：
Shive, Carey;Pandiyan, Pushpa
通讯作者：
Pandiyan, Pushpa

Distinct SARS-CoV-2 specific NLRP3 and IL-1β responses in T cells of aging patients during acute COVID-19 infection.

DOI：
10.3389/fimmu.2023.1231087
发表时间：
2023
期刊：
Frontiers in immunology
影响因子：
7.3
作者：
通讯作者：

Fungal Colonization and Infections-Interactions with Other Human Diseases.

DOI：
10.3390/pathogens11020212
发表时间：
2022-02-06
期刊：
Pathogens (Basel, Switzerland)
影响因子：
0
作者：
Mahalingam SS;Jayaraman S;Pandiyan P
通讯作者：
Pandiyan P

Polyamine metabolism impacts T cell dysfunction in the oral mucosa of people living with HIV.

DOI：
10.1038/s41467-023-36163-2
发表时间：
2023-01-25
期刊：
NATURE COMMUNICATIONS
影响因子：
16.6
作者：
Mahalingam, S. S.;Jayaraman, S.;Bhaskaran, N.;Schneider, E.;Faddoul, F.;da Silva, A. Paes;Lederman, M. M.;Asaad, R.;Adkins-Travis, K.;Shriver, L. P.;Pandiyan, P.
通讯作者：
Pandiyan, P.