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人类皮肤利什曼病中表达组织归巢受体的记忆性T细胞亚群和趋化因子水平

Memory T Cell Subsets Expressing Tissue Homing Receptors and Chemokine Levels in Human Tegumentary Leishmaniasis.

作者信息

Pimentel Julia, García Bustos M Fernanda, Ragone Paula, Marco Jorge D, Barroso Paola, Mesías Andrea Cecilia, Basombrío Mercedes, Occhionero María, Ramos Federico, Laucella Susana Adriana, Pérez Brandán Cecilia, Parodi Cecilia

机构信息

Instituto de Patología Experimental, CONICET/Universidad Nacional de Salta, Salta A4408FVY, Argentina.

Instituto Nacional de Parasitología Dr. Mario Fatala Chaben, Departamento de Investigación, Buenos Aires C1282AFF, Argentina.

出版信息

Cells. 2025 Apr 16;14(8):604. doi: 10.3390/cells14080604.

Abstract

Tegumentary leishmaniasis (TL) presents two main clinical forms: cutaneous (CL) and mucosal (ML) leishmaniasis affecting skin and nasopharyngeal mucosa. Due to parasite localization through disease stages, recruitment of T cells expressing chemokine receptors and their ligands will influence the generated host responses. The aim of this work was to characterize differential profiles of T cells expressing chemokine receptors and their plasma ligands by flow cytometry and ELISA. CL patients showed increased numbers of effector memory CD4 T cells expressing skin homing receptors (CLA, CCR4), with the reversion of this effector phenotype observed after achieving clinical recovery. Meanwhile, ML patients showed higher frequencies of effector memory/terminal effector CD4 and CD8 T cells expressing chemokine receptors directed to skin (CLA, CCR4, CCR10) and mucosal (CCR6) tissues. Additionally, we reported that plasma amounts of ligands (CCL17, CCL20) vary according to the clinical form of TL. Finally, we demonstrated the ability of spp. to modulate chemokine production (CCL17) in vitro. This work highlights the effector T cell response directed to skin and mucosal tissues in TL, emphasizing the role of cytotoxic functions in ML. The studied chemokine receptors could contribute to predicting disease progression and guiding future studies targeting relevant receptors to diminish pathogenic effector functions.

摘要

皮肤利什曼病(TL)呈现两种主要临床形式:皮肤型(CL)和黏膜型(ML)利什曼病,分别影响皮肤和鼻咽黏膜。由于寄生虫在疾病各阶段的定位,表达趋化因子受体及其配体的T细胞募集会影响宿主产生的反应。本研究的目的是通过流式细胞术和酶联免疫吸附测定(ELISA)来表征表达趋化因子受体及其血浆配体的T细胞的差异谱。CL患者中,表达皮肤归巢受体(CLA、CCR4)的效应记忆CD4 T细胞数量增加,临床康复后这种效应表型出现逆转。同时,ML患者中,表达趋化因子受体(CLA、CCR4、CCR10)的效应记忆/终末效应CD4和CD8 T细胞频率更高,这些趋化因子受体分别指向皮肤和黏膜组织(CCR6)。此外,我们报告称,配体(CCL17、CCL20)的血浆量根据TL的临床形式而变化。最后,我们证明了 spp.在体外调节趋化因子产生(CCL17)的能力。这项研究突出了TL中针对皮肤和黏膜组织的效应T细胞反应,强调了细胞毒性功能在ML中的作用。所研究的趋化因子受体可能有助于预测疾病进展,并指导未来针对相关受体的研究,以减少致病性效应功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28aa/12025617/4e139cfecd59/cells-14-00604-g001.jpg

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