Single-cell transcriptome analyses reveal disturbed decidual homoeostasis in obstetric antiphospholipid syndrome
© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ..
OBJECTIVES: Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies in circulation and pathological pregnancy. However, the pathogenesis of OAPS remains unknown. We aimed to reveal cellular compositions and molecular features of decidual cells involved in the development of OAPS using single-cell RNA sequencing (scRNA-seq).
METHODS: We performed unbiased scRNA-seq analysis on the first-trimester decidua from five OAPS patients and five healthy controls (HCs), followed by validations with flow cytometry, immunohistochemical staining and immunofluorescence in a larger cohort. Serum chemokines and cytokines were measured by using ELISA.
RESULTS: A higher ratio of macrophages but a lower ratio of decidual natural killer (dNK) cells was found in decidua from OAPS compared with HCs. Vascular endothelial cells shrinked in OAPS decidua while having upregulated chemokine expression and conspicuous responses to IFN-γ and TNF-α. Macrophages in OAPS had stronger phagocytosis function, complement activation signals and relied more on glycolysis. dNK cells were more activated in OAPS and had enhanced cytotoxicity and IFN-γ production. Downregulation of granules in OAPS dNK cells could be associated with suppressed glycolysis. Moreover, stromal cells had a prosenescent state with weakened immune surveillance for senescent cells in OAPS. In addition, the cellular interactions between decidual immune cells and those of immune cells with non-immune cells under disease state were altered, especially through chemokines, IFN-γ and TNF-α.
CONCLUSION: This study provided a comprehensive decidual cell landscape and identified aberrant decidual microenvironment in OAPS, providing some potential therapeutic targets for this disease.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:83 |
|---|---|
| Enthalten in: |
Annals of the rheumatic diseases - 83(2024), 5 vom: 11. Apr., Seite 624-637 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lu, Chenyang [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antibodies, Antiphospholipid |
|---|
| Anmerkungen: |
Date Completed 15.04.2024 Date Revised 15.04.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1136/ard-2023-224930 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368210731 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368210731 | ||
| 003 | DE-627 | ||
| 005 | 20240415233202.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240209s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1136/ard-2023-224930 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1376.xml |
| 035 | |a (DE-627)NLM368210731 | ||
| 035 | |a (NLM)38331588 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lu, Chenyang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Single-cell transcriptome analyses reveal disturbed decidual homoeostasis in obstetric antiphospholipid syndrome |
| 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 15.04.2024 | ||
| 500 | |a Date Revised 15.04.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a OBJECTIVES: Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies in circulation and pathological pregnancy. However, the pathogenesis of OAPS remains unknown. We aimed to reveal cellular compositions and molecular features of decidual cells involved in the development of OAPS using single-cell RNA sequencing (scRNA-seq) | ||
| 520 | |a METHODS: We performed unbiased scRNA-seq analysis on the first-trimester decidua from five OAPS patients and five healthy controls (HCs), followed by validations with flow cytometry, immunohistochemical staining and immunofluorescence in a larger cohort. Serum chemokines and cytokines were measured by using ELISA | ||
| 520 | |a RESULTS: A higher ratio of macrophages but a lower ratio of decidual natural killer (dNK) cells was found in decidua from OAPS compared with HCs. Vascular endothelial cells shrinked in OAPS decidua while having upregulated chemokine expression and conspicuous responses to IFN-γ and TNF-α. Macrophages in OAPS had stronger phagocytosis function, complement activation signals and relied more on glycolysis. dNK cells were more activated in OAPS and had enhanced cytotoxicity and IFN-γ production. Downregulation of granules in OAPS dNK cells could be associated with suppressed glycolysis. Moreover, stromal cells had a prosenescent state with weakened immune surveillance for senescent cells in OAPS. In addition, the cellular interactions between decidual immune cells and those of immune cells with non-immune cells under disease state were altered, especially through chemokines, IFN-γ and TNF-α | ||
| 520 | |a CONCLUSION: This study provided a comprehensive decidual cell landscape and identified aberrant decidual microenvironment in OAPS, providing some potential therapeutic targets for this disease | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Antibodies, Antiphospholipid | |
| 650 | 4 | |a Antiphospholipid Syndrome | |
| 650 | 4 | |a Autoimmune Diseases | |
| 650 | 4 | |a Autoimmunity | |
| 650 | 4 | |a Inflammation | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 650 | 7 | |a Chemokines |2 NLM | |
| 700 | 1 | |a Gao, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Qing, Pingying |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Xun |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Lang |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Annals of the rheumatic diseases |d 1939 |g 83(2024), 5 vom: 11. Apr., Seite 624-637 |w (DE-627)NLM000174114 |x 1468-2060 |7 nnns |
| 773 | 1 | 8 | |g volume:83 |g year:2024 |g number:5 |g day:11 |g month:04 |g pages:624-637 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1136/ard-2023-224930 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 83 |j 2024 |e 5 |b 11 |c 04 |h 624-637 | ||