Pathogenic accumulation of T follicular helper cells in lupus disease depends on PD-L1 and IL-4 expressing basophils
ABSTRACT Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies raised against nuclear antigens and whose production is promoted by autoreactive T follicular helper (TFH) cells. Basophils, by accumulating in secondary lymphoid organs (SLO), amplify autoantibody production and disease progression through mechanisms to be defined. Here, we demonstrate that a functional relationship between TFH cells and basophils occurs in SLO during lupus pathogenesis. On SLE patient blood basophils, PD-L1 expression was upregulated and associated with TFH and TFH2 cell expansions and with disease activity. In two distinct lupus-like mouse models, TFH cell pathogenic accumulation, maintenance and function, and disease activity were dependent on basophils and their expressions of PD-L1 and IL-4. Our study establishes a direct link between basophils and TFH cells in the SLE context that promotes autoreactive IgG production and lupus nephritis pathogenesis. Altering the basophil/TFH cell axis in the SLE context may represent a promising innovative intervention strategy in SLE..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 04. Dez. Zur Gesamtaufnahme - year:2023 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Tchen, John [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.1101/2023.01.10.23284399 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI038392151 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI038392151 | ||
| 003 | DE-627 | ||
| 005 | 20231205091452.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230112s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2023.01.10.23284399 |2 doi | |
| 035 | |a (DE-627)XBI038392151 | ||
| 035 | |a (biorXiv)10.1101/2023.01.10.23284399 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Tchen, John |e verfasserin |0 (orcid)0000-0001-6474-6790 |4 aut | |
| 245 | 1 | 0 | |a Pathogenic accumulation of T follicular helper cells in lupus disease depends on PD-L1 and IL-4 expressing basophils |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a ABSTRACT Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies raised against nuclear antigens and whose production is promoted by autoreactive T follicular helper (TFH) cells. Basophils, by accumulating in secondary lymphoid organs (SLO), amplify autoantibody production and disease progression through mechanisms to be defined. Here, we demonstrate that a functional relationship between TFH cells and basophils occurs in SLO during lupus pathogenesis. On SLE patient blood basophils, PD-L1 expression was upregulated and associated with TFH and TFH2 cell expansions and with disease activity. In two distinct lupus-like mouse models, TFH cell pathogenic accumulation, maintenance and function, and disease activity were dependent on basophils and their expressions of PD-L1 and IL-4. Our study establishes a direct link between basophils and TFH cells in the SLE context that promotes autoreactive IgG production and lupus nephritis pathogenesis. Altering the basophil/TFH cell axis in the SLE context may represent a promising innovative intervention strategy in SLE. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Simon, Quentin |0 (orcid)0000-0002-2383-2809 |4 aut | |
| 700 | 1 | |a Chapart, Léa |4 aut | |
| 700 | 1 | |a Lamri, Yasmine |4 aut | |
| 700 | 1 | |a Saidoune, Fanny |4 aut | |
| 700 | 1 | |a Pacreau, Emeline |0 (orcid)0000-0001-6289-3869 |4 aut | |
| 700 | 1 | |a Pellefigues, Christophe |0 (orcid)0000-0001-7036-0763 |4 aut | |
| 700 | 1 | |a Bex-Coudrat, Julie |4 aut | |
| 700 | 1 | |a Karasuyama, Hajime |0 (orcid)0000-0003-0689-0836 |4 aut | |
| 700 | 1 | |a Miyake, Kensuke |0 (orcid)0000-0003-1149-3755 |4 aut | |
| 700 | 1 | |a Hidalgo, Juan |0 (orcid)0000-0003-0921-1122 |4 aut | |
| 700 | 1 | |a Fallon, Padraic G. |0 (orcid)0000-0002-8401-7293 |4 aut | |
| 700 | 1 | |a Papo, Thomas |0 (orcid)0000-0002-7481-5099 |4 aut | |
| 700 | 1 | |a Blank, Ulrich |0 (orcid)0000-0002-2661-2983 |4 aut | |
| 700 | 1 | |a Benhamou, Marc |0 (orcid)0000-0001-7763-3795 |4 aut | |
| 700 | 1 | |a Hanouna, Guillaume |0 (orcid)0000-0002-3902-0119 |4 aut | |
| 700 | 1 | |a Sacre, Karim |0 (orcid)0000-0002-6544-234X |4 aut | |
| 700 | 1 | |a Daugas, Eric |0 (orcid)0000-0001-7256-7979 |4 aut | |
| 700 | 1 | |a Charles, Nicolas |0 (orcid)0000-0002-5416-5834 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2023) vom: 04. Dez. |
| 773 | 1 | 8 | |g year:2023 |g day:04 |g month:12 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2023.01.10.23284399 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 951 | |a AR | ||
| 952 | |j 2023 |b 04 |c 12 | ||