HERV1-env Induces Unfolded Protein Response Activation in Autoimmune Liver Disease : A Potential Mechanism for Regulatory T Cell Dysfunction
Copyright © 2023 by The American Association of Immunologists, Inc..
Regulatory T cells (Tregs) are not terminally differentiated but can acquire effector properties. Here we report an increased expression of human endogenous retrovirus 1 (HERV1-env) proteins in Tregs of patients with de novo autoimmune hepatitis and autoimmune hepatitis, which induces endoplasmic reticulum (ER) stress. HERV1-env-triggered ER stress activates all three branches (IRE1, ATF6, and PERK) of the unfolded protein response (UPR). Our coimmunoprecipitation studies show an interaction between HERV1-env proteins and the ATF6 branch of the UPR. The activated form of ATF6α activates the expression of RORC and STAT3 by binding to promoter sequences and induces IL-17A production. Silencing of HERV1-env results in recovery of Treg suppressive function. These findings identify ER stress and UPR activation as key factors driving Treg plasticity (species: human).
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:210 |
|---|---|
| Enthalten in: |
Journal of immunology (Baltimore, Md. : 1950) - 210(2023), 6 vom: 15. März, Seite 732-744 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Subramanian, Kumar [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Activating Transcription Factor 6 |
|---|
| Anmerkungen: |
Date Completed 09.03.2023 Date Revised 16.03.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.4049/jimmunol.2100186 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM352332859 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM352332859 | ||
| 003 | DE-627 | ||
| 005 | 20240316232454.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.4049/jimmunol.2100186 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1332.xml |
| 035 | |a (DE-627)NLM352332859 | ||
| 035 | |a (NLM)36722941 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Subramanian, Kumar |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a HERV1-env Induces Unfolded Protein Response Activation in Autoimmune Liver Disease |b A Potential Mechanism for Regulatory T Cell Dysfunction |
| 264 | 1 | |c 2023 | |
| 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 09.03.2023 | ||
| 500 | |a Date Revised 16.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 by The American Association of Immunologists, Inc. | ||
| 520 | |a Regulatory T cells (Tregs) are not terminally differentiated but can acquire effector properties. Here we report an increased expression of human endogenous retrovirus 1 (HERV1-env) proteins in Tregs of patients with de novo autoimmune hepatitis and autoimmune hepatitis, which induces endoplasmic reticulum (ER) stress. HERV1-env-triggered ER stress activates all three branches (IRE1, ATF6, and PERK) of the unfolded protein response (UPR). Our coimmunoprecipitation studies show an interaction between HERV1-env proteins and the ATF6 branch of the UPR. The activated form of ATF6α activates the expression of RORC and STAT3 by binding to promoter sequences and induces IL-17A production. Silencing of HERV1-env results in recovery of Treg suppressive function. These findings identify ER stress and UPR activation as key factors driving Treg plasticity (species: human) | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a eIF-2 Kinase |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Activating Transcription Factor 6 |2 NLM | |
| 700 | 1 | |a Paul, Saikat |e verfasserin |4 aut | |
| 700 | 1 | |a Libby, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Patterson, Jordan |e verfasserin |4 aut | |
| 700 | 1 | |a Arterbery, Adam |e verfasserin |4 aut | |
| 700 | 1 | |a Knight, James |e verfasserin |4 aut | |
| 700 | 1 | |a Castaldi, Christopher |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Guilin |e verfasserin |4 aut | |
| 700 | 1 | |a Avitzur, Yaron |e verfasserin |4 aut | |
| 700 | 1 | |a Martinez, Mercedes |e verfasserin |4 aut | |
| 700 | 1 | |a Lobritto, Steve |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Yanhong |e verfasserin |4 aut | |
| 700 | 1 | |a Geliang, Gan |e verfasserin |4 aut | |
| 700 | 1 | |a Kroemer, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Fishbein, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Mason, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Dominguez-Villar, Margarita |e verfasserin |4 aut | |
| 700 | 1 | |a Mariappan, Malaiyalam |e verfasserin |4 aut | |
| 700 | 1 | |a Ekong, Udeme D |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of immunology (Baltimore, Md. : 1950) |d 1945 |g 210(2023), 6 vom: 15. März, Seite 732-744 |w (DE-627)NLM000018554 |x 1550-6606 |7 nnns |
| 773 | 1 | 8 | |g volume:210 |g year:2023 |g number:6 |g day:15 |g month:03 |g pages:732-744 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.4049/jimmunol.2100186 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 210 |j 2023 |e 6 |b 15 |c 03 |h 732-744 | ||