Titre :

Altered b lymphocyte homeostasis and functions in systemic sclerosis

Auteur(s) :

Forestier, Alexandra [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Guerrier, Thomas [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Jouvray, Mathieu [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Giovannelli, Jonathan [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lefevre, Guillaume [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Sobanski, Vincent [Auteur]
Lille Inflammation Research International Center (LIRIC) - U995
Hauspie, Carine [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Hachulla, Eric [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Hatron, Pierre-Yves [Auteur]
ZEPHIR, Helene [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Vermersch, Patrick [Auteur]
Lille Inflammation Research International Center (LIRIC) - U995
Labalette, Myriam [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Launay, David [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Dubucquoi, Sylvain [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]

Titre de la revue :

Autoimmunity Reviews

Nom court de la revue :

Autoimmun Rev

Numéro :

17

Pagination :

244-255

Date de publication :

2018-03

ISSN :

1873-0183

Mot(s)-clé(s) :

Systemic sclerosis
Signaling pathways
IL-6
IL-10
B-cells

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Beyond the production of autoantibodies, B-cells are thought to play a role in systemic sclerosis (SSc) by secreting proinflammatory/profibrotic cytokines. B-cells are a heterogeneous population with different subsets ...
Lire la suite >Beyond the production of autoantibodies, B-cells are thought to play a role in systemic sclerosis (SSc) by secreting proinflammatory/profibrotic cytokines. B-cells are a heterogeneous population with different subsets distinguished by their phenotypes and cytokine production. Data about B-cell subsets, cytokine production and intracellular pathways leading to this production are scarce in SSc. The aim of our study was to describe B-cell homeostasis, activation, proliferation, cytokine production in B-cells and serum and B-cell intracellular signaling pathways in SSc. We hypothezided that B-cell homeostasis and cytokine production were altered in SSc and could be explained by serum cytokine as well as by intracellular signaling pathway abnormalities. Forty SSc patients and 20 healthy controls (HC) were prospectively included. B-cell subsets were determined by flow cytometry using CD19, CD21, CD24, CD38, CD27, IgM and IgD. CD25, CD80, CD95, HLA-DR were used to assess B-cell activation. Intracellular production of IL-10 and IL-6 were assessed by flow cytometry after TLR9 and CD40 stimulation. IL-6, IL-10, Ki67, Bcl2 mRNA were quantified in B-cells. Cytokine production was also assessed in sera and supernatants of B-cell culture, using a multiplex approach. Signaling pathways were studied through phosphorylation of mTOR, ERK, STAT3, STAT5 using a flow cytometry approach. We found that SSc patients exhibited an altered peripheral blood B-cell subset distribution, with decreased memory B-cells but increased proportion of naive and CD21LoCD38Lo B-cell subsets. We observed an increased expression of activation markers (CD80, CD95, HLA-DR) on some B-cell subsets, mainly the memory B-cells. Secretion of IL-6, BAFF and CXCL13 were increased in SSc sera. There was no correlation between the peripheral blood B-cell subsets and the serum concentrations of these cytokines. After stimulation, we observed a lower proportion of IL-10 and IL-6 producing B–cells in SSc. Finally, we observed a significant decrease of mTOR phosphorylation in SSc patient B-cells. In conclusion, we observed an altered B-cell homeostasis in SSc patients compared to HC. Memory B-cells were both decreased and activated in patients. IL-10 producing B-cells were decreased in SSc. This decrease was associated with an alteration of mTOR phosphorylation in B-cells. Conversely, there was no correlation between serum cytokine profile and B-cell homeostasis alterations.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
• Lille Neurosciences & Cognition (LilNCog) - U 1172

Équipe(s) de recherche :

Neuroinflammation & Multiple Sclerosis (NEMESIS)

Date de dépôt :

2021-06-23T11:45:03Z
2024-01-25T12:43:07Z