IL-10 critically modulates B cell responsiveness in rankl-/- mice

Veronica Marrella, Nadia Lo Iacono, Elena Fontana, Cristina Sobacchi, Heiko Sic, Francesca Schena, Lucia Sereni, Maria Carmina Castiello, Pietro Luigi Poliani, Paolo Vezzoni, Barbara Cassani, Elisabetta Traggiai, Anna Villa

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The immune and the skeletal system are tightly interconnected, and B lymphocytes are uniquely endowed with osteo-interactive properties. In this context, receptor activator of NF-κB (RANK) ligand (RANKL) plays a pivotal role in lymphoid tissue formation and bone homeostasis. Although murine models lacking RANK or RANKL show defects in B cell number, the role of the RANKL-RANK axis on B physiology is still a matter of debate. In this study, we have characterized in detail B cell compartment in Rankl-/- mice, finding a relative expansion of marginal zone B cells, B1 cells, and plasma cells associated with increased Ig serum levels, spontaneous germinal center formation, and hyperresponse to CD40 triggering. Such abnormalities were associated with an increased frequency of regulatory B cells and augmented B cell-derived IL-10 production. Remarkably, in vivo IL-10-R blockade reduced T cell-triggered plasma cell differentiation and restrained the expansion of regulatory B cells. These data point to a novel role of the RANKL-RANK axis in the regulation of B cell homeostasis and highlight an unexpected link between IL-10 CD40 signaling and the RANKL pathway.

Original languageEnglish
Pages (from-to)4144-4153
Number of pages10
JournalJournal of Immunology
Volume194
Issue number9
DOIs
Publication statusPublished - May 1 2015

Fingerprint

RANK Ligand
Interleukin-10
B-Lymphocytes
Regulatory B-Lymphocytes
Plasma Cells
Homeostasis
Germinal Center
Lymphoid Tissue
Osteogenesis
Cell Differentiation
Immune System
Cell Count
T-Lymphocytes
Serum

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

IL-10 critically modulates B cell responsiveness in rankl-/- mice. / Marrella, Veronica; Lo Iacono, Nadia; Fontana, Elena; Sobacchi, Cristina; Sic, Heiko; Schena, Francesca; Sereni, Lucia; Castiello, Maria Carmina; Poliani, Pietro Luigi; Vezzoni, Paolo; Cassani, Barbara; Traggiai, Elisabetta; Villa, Anna.

In: Journal of Immunology, Vol. 194, No. 9, 01.05.2015, p. 4144-4153.

Research output: Contribution to journalArticle

Marrella, Veronica ; Lo Iacono, Nadia ; Fontana, Elena ; Sobacchi, Cristina ; Sic, Heiko ; Schena, Francesca ; Sereni, Lucia ; Castiello, Maria Carmina ; Poliani, Pietro Luigi ; Vezzoni, Paolo ; Cassani, Barbara ; Traggiai, Elisabetta ; Villa, Anna. / IL-10 critically modulates B cell responsiveness in rankl-/- mice. In: Journal of Immunology. 2015 ; Vol. 194, No. 9. pp. 4144-4153.
@article{fe4714b2183b41a0aca44842422f8000,
title = "IL-10 critically modulates B cell responsiveness in rankl-/- mice",
abstract = "The immune and the skeletal system are tightly interconnected, and B lymphocytes are uniquely endowed with osteo-interactive properties. In this context, receptor activator of NF-κB (RANK) ligand (RANKL) plays a pivotal role in lymphoid tissue formation and bone homeostasis. Although murine models lacking RANK or RANKL show defects in B cell number, the role of the RANKL-RANK axis on B physiology is still a matter of debate. In this study, we have characterized in detail B cell compartment in Rankl-/- mice, finding a relative expansion of marginal zone B cells, B1 cells, and plasma cells associated with increased Ig serum levels, spontaneous germinal center formation, and hyperresponse to CD40 triggering. Such abnormalities were associated with an increased frequency of regulatory B cells and augmented B cell-derived IL-10 production. Remarkably, in vivo IL-10-R blockade reduced T cell-triggered plasma cell differentiation and restrained the expansion of regulatory B cells. These data point to a novel role of the RANKL-RANK axis in the regulation of B cell homeostasis and highlight an unexpected link between IL-10 CD40 signaling and the RANKL pathway.",
author = "Veronica Marrella and {Lo Iacono}, Nadia and Elena Fontana and Cristina Sobacchi and Heiko Sic and Francesca Schena and Lucia Sereni and Castiello, {Maria Carmina} and Poliani, {Pietro Luigi} and Paolo Vezzoni and Barbara Cassani and Elisabetta Traggiai and Anna Villa",
year = "2015",
month = "5",
day = "1",
doi = "10.4049/jimmunol.1401977",
language = "English",
volume = "194",
pages = "4144--4153",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

TY - JOUR

T1 - IL-10 critically modulates B cell responsiveness in rankl-/- mice

AU - Marrella, Veronica

AU - Lo Iacono, Nadia

AU - Fontana, Elena

AU - Sobacchi, Cristina

AU - Sic, Heiko

AU - Schena, Francesca

AU - Sereni, Lucia

AU - Castiello, Maria Carmina

AU - Poliani, Pietro Luigi

AU - Vezzoni, Paolo

AU - Cassani, Barbara

AU - Traggiai, Elisabetta

AU - Villa, Anna

PY - 2015/5/1

Y1 - 2015/5/1

N2 - The immune and the skeletal system are tightly interconnected, and B lymphocytes are uniquely endowed with osteo-interactive properties. In this context, receptor activator of NF-κB (RANK) ligand (RANKL) plays a pivotal role in lymphoid tissue formation and bone homeostasis. Although murine models lacking RANK or RANKL show defects in B cell number, the role of the RANKL-RANK axis on B physiology is still a matter of debate. In this study, we have characterized in detail B cell compartment in Rankl-/- mice, finding a relative expansion of marginal zone B cells, B1 cells, and plasma cells associated with increased Ig serum levels, spontaneous germinal center formation, and hyperresponse to CD40 triggering. Such abnormalities were associated with an increased frequency of regulatory B cells and augmented B cell-derived IL-10 production. Remarkably, in vivo IL-10-R blockade reduced T cell-triggered plasma cell differentiation and restrained the expansion of regulatory B cells. These data point to a novel role of the RANKL-RANK axis in the regulation of B cell homeostasis and highlight an unexpected link between IL-10 CD40 signaling and the RANKL pathway.

AB - The immune and the skeletal system are tightly interconnected, and B lymphocytes are uniquely endowed with osteo-interactive properties. In this context, receptor activator of NF-κB (RANK) ligand (RANKL) plays a pivotal role in lymphoid tissue formation and bone homeostasis. Although murine models lacking RANK or RANKL show defects in B cell number, the role of the RANKL-RANK axis on B physiology is still a matter of debate. In this study, we have characterized in detail B cell compartment in Rankl-/- mice, finding a relative expansion of marginal zone B cells, B1 cells, and plasma cells associated with increased Ig serum levels, spontaneous germinal center formation, and hyperresponse to CD40 triggering. Such abnormalities were associated with an increased frequency of regulatory B cells and augmented B cell-derived IL-10 production. Remarkably, in vivo IL-10-R blockade reduced T cell-triggered plasma cell differentiation and restrained the expansion of regulatory B cells. These data point to a novel role of the RANKL-RANK axis in the regulation of B cell homeostasis and highlight an unexpected link between IL-10 CD40 signaling and the RANKL pathway.

UR - http://www.scopus.com/inward/record.url?scp=84928501037&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928501037&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1401977

DO - 10.4049/jimmunol.1401977

M3 - Article

C2 - 25825446

AN - SCOPUS:84928501037

VL - 194

SP - 4144

EP - 4153

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -