Exosomes containing long non-coding RNA AGAP2-AS1 promote the differentiation of CD4+ T cells through the miR-424-5p/SGK1 axis in psoriasis

BackgroundLong non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of autoimmune diseases. Our previous research demonstrated that AGAP2-AS1 in keratinocytes is involved in the pathogenesis of psoriasis, but its effect on CD4+ T cell differentiation remains unclear.MethodsExosomes wer...

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Main Authors: Ziqi Yuan, Xue Zeng, Xiwei Zhang, Chenglai Xia, Xuebiao Peng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Genetics
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Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2025.1521470/full
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author Ziqi Yuan
Xue Zeng
Xiwei Zhang
Chenglai Xia
Xuebiao Peng
author_facet Ziqi Yuan
Xue Zeng
Xiwei Zhang
Chenglai Xia
Xuebiao Peng
author_sort Ziqi Yuan
collection DOAJ
description BackgroundLong non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of autoimmune diseases. Our previous research demonstrated that AGAP2-AS1 in keratinocytes is involved in the pathogenesis of psoriasis, but its effect on CD4+ T cell differentiation remains unclear.MethodsExosomes were extracted from HaCaT cells using a reagent kit and verified by TEM (Transmission Electron Microscope), NTA (Nanoparticle Tracking Analysis), and Western Blot. We incubated exosomes with CD4+ T cells and detected the distribution of AGAP2-AS1 by fluorescence microscopy. Flow cytometry and ELISA were used to detect CD4+ T cell differentiation. In addition, the relationship between AGAP2-AS1/miR-424-5p/SGK1 and its effect on CD4+ T cell differentiation were confirmed by bioinformatics analysis, dual luciferase reporter gene experiments, quantitative real-time PCR, flow cytometry, and ELISA.ResultsWe found that exosomes derived from TNF-α-treated HaCaTs were able to deliver AGAP2-AS1 to CD4+ T cells, promoting Th1 and Th17 differentiation. In CD4+ T cells, AGAP2-AS1 promotes Th1 and Th17 differentiation via the miR-424-5p/SGK1 axis.ConclusionPsoriatic HaCaTs deliver AGAP2-AS1 to CD4+ T cells via exosomes, inducing Th1 and Th17 differentiation through the miR-424-5p/SGK1 axis, thereby promoting the progression of psoriasis. These findings provide novel insights into the pathogenesis of psoriasis and potential therapeutic targets.
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spelling doaj-art-e21a2cc0b92c4636850220db8f9aad962025-08-20T03:21:34ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-05-011610.3389/fgene.2025.15214701521470Exosomes containing long non-coding RNA AGAP2-AS1 promote the differentiation of CD4+ T cells through the miR-424-5p/SGK1 axis in psoriasisZiqi Yuan0Xue Zeng1Xiwei Zhang2Chenglai Xia3Xuebiao Peng4Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaFoshan Maternity and Child Healthcare Hospital, Foshan, ChinaDepartment of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaBackgroundLong non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of autoimmune diseases. Our previous research demonstrated that AGAP2-AS1 in keratinocytes is involved in the pathogenesis of psoriasis, but its effect on CD4+ T cell differentiation remains unclear.MethodsExosomes were extracted from HaCaT cells using a reagent kit and verified by TEM (Transmission Electron Microscope), NTA (Nanoparticle Tracking Analysis), and Western Blot. We incubated exosomes with CD4+ T cells and detected the distribution of AGAP2-AS1 by fluorescence microscopy. Flow cytometry and ELISA were used to detect CD4+ T cell differentiation. In addition, the relationship between AGAP2-AS1/miR-424-5p/SGK1 and its effect on CD4+ T cell differentiation were confirmed by bioinformatics analysis, dual luciferase reporter gene experiments, quantitative real-time PCR, flow cytometry, and ELISA.ResultsWe found that exosomes derived from TNF-α-treated HaCaTs were able to deliver AGAP2-AS1 to CD4+ T cells, promoting Th1 and Th17 differentiation. In CD4+ T cells, AGAP2-AS1 promotes Th1 and Th17 differentiation via the miR-424-5p/SGK1 axis.ConclusionPsoriatic HaCaTs deliver AGAP2-AS1 to CD4+ T cells via exosomes, inducing Th1 and Th17 differentiation through the miR-424-5p/SGK1 axis, thereby promoting the progression of psoriasis. These findings provide novel insights into the pathogenesis of psoriasis and potential therapeutic targets.https://www.frontiersin.org/articles/10.3389/fgene.2025.1521470/fulllong non-coding RNAsmicrornaspsoriasist cellsexosomes
spellingShingle Ziqi Yuan
Xue Zeng
Xiwei Zhang
Chenglai Xia
Xuebiao Peng
Exosomes containing long non-coding RNA AGAP2-AS1 promote the differentiation of CD4+ T cells through the miR-424-5p/SGK1 axis in psoriasis
Frontiers in Genetics
long non-coding RNAs
micrornas
psoriasis
t cells
exosomes
title Exosomes containing long non-coding RNA AGAP2-AS1 promote the differentiation of CD4+ T cells through the miR-424-5p/SGK1 axis in psoriasis
title_full Exosomes containing long non-coding RNA AGAP2-AS1 promote the differentiation of CD4+ T cells through the miR-424-5p/SGK1 axis in psoriasis
title_fullStr Exosomes containing long non-coding RNA AGAP2-AS1 promote the differentiation of CD4+ T cells through the miR-424-5p/SGK1 axis in psoriasis
title_full_unstemmed Exosomes containing long non-coding RNA AGAP2-AS1 promote the differentiation of CD4+ T cells through the miR-424-5p/SGK1 axis in psoriasis
title_short Exosomes containing long non-coding RNA AGAP2-AS1 promote the differentiation of CD4+ T cells through the miR-424-5p/SGK1 axis in psoriasis
title_sort exosomes containing long non coding rna agap2 as1 promote the differentiation of cd4 t cells through the mir 424 5p sgk1 axis in psoriasis
topic long non-coding RNAs
micrornas
psoriasis
t cells
exosomes
url https://www.frontiersin.org/articles/10.3389/fgene.2025.1521470/full
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