Artículo
PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment
Zacca, Estefanía
; Onofrio, Luisina Inés
; Acosta, Cristina del Valle; Ferrero, Paola Virginia; Alonso, Sergio Manuel; Ramello, María Cecilia
; Mussano, Eduardo Daniel Eugenio; Onetti, Laura; Cadile, Isaac I.; Stancich, Maria I.; Bonfanti, Maria C. Taboada; Montes, Carolina Lucia
; Acosta Rodriguez, Eva Virginia
; Gruppi, Adriana
Fecha de publicación:
10/2018
Editorial:
Frontiers Media S.A.
Revista:
Frontiers in Immunology
ISSN:
1664-3224
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Background: B cells play an important role in the development and maintenance of rheumatoid arthritis (RA). Although IL-10-producing B cells represent a major subset of regulatory B cells (Bregs) able to suppress autoimmune and inflammatory responses, recent reports showed that B cell-mediated immune suppression may also occur independent of IL-10. For instance, B cells can modulate T cell immune responses through the expression of regulatory molecules such as PD-L1. So far, PD-L1-expressing B cells have not been analyzed in RA patients. Objective: To analyze the frequency of PD-L1-expressing B cells in the peripheral blood of RA patients compared to healthy controls (HC) matched for sex and age, their function on T cell response and their changes in response to therapy. Methods: Fresh peripheral blood B cells from RA patients and HC were characterized by flow cytometry and their functionality assessed in a co-culture system with autologous T cells. Results: The frequencies of CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells were significantly lower in untreated RA patients than in HC. In a follow-up study, the frequencies of PD-L1+ B cells (CD19+PD-L1+ B cells, CD24hiCD38-PD-L1+ and CD24hiCD38hiPD-L1+ B cells) increased significantly after treatment in good responder patients, although the frequency of total CD24hiCD38hi B cells decreased. CD19+ B cells from untreated RA patients and HC upregulated PD-L1 expression similarly upon stimulation with CpG plus IL-2 and were able to suppress, in vitro, CD8+ T cell proliferation and cytokine production in a PD-L1-dependent manner. Conclusions: Our results show that PD-L1+ B cells exhibiting T cell suppressive capacity are significantly decreased in untreated RA patients but increase in response to successful treatment. PD-L1 expression on B cells from RA patients can be modulated in vitro and PD-L1+ B cells could thus provide new perspectives for future treatment strategies.
Palabras clave:
BREGS
,
INFLAMMATION
,
PD-L1
,
RHEUMATIC DISEASES
,
RHEUMATOID ARTHRITIS
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Identificadores
Colecciones
Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Citación
Zacca, Estefanía; Onofrio, Luisina Inés; Acosta, Cristina del Valle; Ferrero, Paola Virginia; Alonso, Sergio Manuel; et al.; PD-L1+ Regulatory B Cells Are Significantly Decreased in Rheumatoid Arthritis Patients and Increase After Successful Treatment; Frontiers Media S.A.; Frontiers in Immunology; 9; 10-2018; 1-13
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