Keratinocyte-to-macrophage communication exacerbate psoriasiform dermatitis via LRG1-enriched extracellular vesicles
© The author(s)..
Rationale: Macrophage-associated inflammation and keratinocytes excessive proliferation and inflammatory cytokines secretion induced by stimulation play an important role in the progression of psoriasiform dermatitis. However, how these two types of cells communicate remains obscure. Methods: We induced a mouse model with experimental psoriasiform dermatitis by Imiquimod (IMQ). To investigate whether damaged keratinocytes promote macrophage polarization and accelerate skin lesions by releasing extracellular vesicle (EV), purified EV were isolated from the primary epidermis of 5-day IMQ-induced psoriasiform dermatitis model mice, and then fluorescence-labeled the EV with PKH67. The EV was injected into the skin of mice treated with IMQ or vehicle 2 days in situ. In addition, we established a co-culture system of the human monocytic cell line (THP-1) and HaCaT, and THP-1/HaCaT conditioned media culture model in vitro respectively. Subsequently, we evaluated the effect of Leucine-rich α-2-glycoprotein 1 (LRG1)-enriched EV on macrophage activation. Results: We demonstrated macrophages can significantly promote keratinocyte inflammation and macrophage polarization may be mediated by intercellular communication with keratinocytes. Interestingly, IMQ-induced 5-day, keratinocyte-derived EV recruited macrophage and enhanced the progression of skin lesions. Similar to results in vivo, EV released from M5-treated HaCaT significantly promotes Interleukin 1β (IL-1β) and Tumor necrosis factor α (TNF-α) expression of THP-1 cells. Importantly, we found that LRG1-enriched EV regulates macrophages via TGF beta Receptor 1 (TGFβR1) dependent process. Conclusion: Our findings indicated a novel mechanism for promoting psoriasiform dermatitis, which could be a potential therapeutic target.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
---|---|
Enthalten in: |
Theranostics - 14(2024), 3 vom: 17., Seite 1049-1064 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Jiang, Wenjuan [VerfasserIn] |
---|
Links: |
---|
Themen: |
Extracellular vesicle |
---|
Anmerkungen: |
Date Completed 23.01.2024 Date Revised 12.02.2024 published: Electronic-eCollection Citation Status MEDLINE |
---|
doi: |
10.7150/thno.89180 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM367405342 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM367405342 | ||
003 | DE-627 | ||
005 | 20240212232050.0 | ||
007 | cr uuu---uuuuu | ||
008 | 240122s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.7150/thno.89180 |2 doi | |
028 | 5 | 2 | |a pubmed24n1289.xml |
035 | |a (DE-627)NLM367405342 | ||
035 | |a (NLM)38250043 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Jiang, Wenjuan |e verfasserin |4 aut | |
245 | 1 | 0 | |a Keratinocyte-to-macrophage communication exacerbate psoriasiform dermatitis via LRG1-enriched extracellular vesicles |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 23.01.2024 | ||
500 | |a Date Revised 12.02.2024 | ||
500 | |a published: Electronic-eCollection | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © The author(s). | ||
520 | |a Rationale: Macrophage-associated inflammation and keratinocytes excessive proliferation and inflammatory cytokines secretion induced by stimulation play an important role in the progression of psoriasiform dermatitis. However, how these two types of cells communicate remains obscure. Methods: We induced a mouse model with experimental psoriasiform dermatitis by Imiquimod (IMQ). To investigate whether damaged keratinocytes promote macrophage polarization and accelerate skin lesions by releasing extracellular vesicle (EV), purified EV were isolated from the primary epidermis of 5-day IMQ-induced psoriasiform dermatitis model mice, and then fluorescence-labeled the EV with PKH67. The EV was injected into the skin of mice treated with IMQ or vehicle 2 days in situ. In addition, we established a co-culture system of the human monocytic cell line (THP-1) and HaCaT, and THP-1/HaCaT conditioned media culture model in vitro respectively. Subsequently, we evaluated the effect of Leucine-rich α-2-glycoprotein 1 (LRG1)-enriched EV on macrophage activation. Results: We demonstrated macrophages can significantly promote keratinocyte inflammation and macrophage polarization may be mediated by intercellular communication with keratinocytes. Interestingly, IMQ-induced 5-day, keratinocyte-derived EV recruited macrophage and enhanced the progression of skin lesions. Similar to results in vivo, EV released from M5-treated HaCaT significantly promotes Interleukin 1β (IL-1β) and Tumor necrosis factor α (TNF-α) expression of THP-1 cells. Importantly, we found that LRG1-enriched EV regulates macrophages via TGF beta Receptor 1 (TGFβR1) dependent process. Conclusion: Our findings indicated a novel mechanism for promoting psoriasiform dermatitis, which could be a potential therapeutic target | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Extracellular vesicle | |
650 | 4 | |a Keratinocyte. | |
650 | 4 | |a Leucine-rich α-2-glycoprotein 1 | |
650 | 4 | |a Macrophage | |
650 | 4 | |a Psoriasis | |
650 | 7 | |a Glycoproteins |2 NLM | |
650 | 7 | |a LRG1 protein, human |2 NLM | |
650 | 7 | |a LRG1 protein, mouse |2 NLM | |
700 | 1 | |a Zhang, Tingting |e verfasserin |4 aut | |
700 | 1 | |a Qiu, Yueqi |e verfasserin |4 aut | |
700 | 1 | |a Liu, Qianmei |e verfasserin |4 aut | |
700 | 1 | |a Chen, Xiaoyun |e verfasserin |4 aut | |
700 | 1 | |a Wang, Qiaolin |e verfasserin |4 aut | |
700 | 1 | |a Min, Xiaoli |e verfasserin |4 aut | |
700 | 1 | |a Ouyang, Lianlian |e verfasserin |4 aut | |
700 | 1 | |a Jia, Sujie |e verfasserin |4 aut | |
700 | 1 | |a Lu, Qianjin |e verfasserin |4 aut | |
700 | 1 | |a He, Yuan |e verfasserin |4 aut | |
700 | 1 | |a Zhao, Ming |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Theranostics |d 2011 |g 14(2024), 3 vom: 17., Seite 1049-1064 |w (DE-627)NLM20717458X |x 1838-7640 |7 nnns |
773 | 1 | 8 | |g volume:14 |g year:2024 |g number:3 |g day:17 |g pages:1049-1064 |
856 | 4 | 0 | |u http://dx.doi.org/10.7150/thno.89180 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 14 |j 2024 |e 3 |b 17 |h 1049-1064 |