Innate pro-B cell progenitors protect against type 1 diabetes by regulating autoimmune effector T cells. - Archive ouverte HAL Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2013

Innate pro-B cell progenitors protect against type 1 diabetes by regulating autoimmune effector T cells.

Abstract

Diverse hematopoietic progenitors, including myeloid populations arising in inflammatory and tumoral conditions and multipotent cells, mobilized by hematopoietic growth factors or emerging during parasitic infections, display tolerogenic properties. Innate immune stimuli confer regulatory functions to various mature B-cell subsets but immature B-cell progenitors endowed with suppressive properties per se or after differentiating into more mature regulatory B cells remain to be characterized. Herein we provide evidence for innate pro-B cells (CpG-proBs) that emerged within the bone marrow both in vitro and in vivo upon Toll-like receptor-9 activation and whose adoptive transfer protected nonobese diabetic mice against type 1 diabetes (T1D). These cells responded to IFN-gamma released by activated effector T cells (Teffs), by up-regulating their Fas ligand (FasL) expression, which enabled them to kill Teffs through apoptosis. In turn, IFN-gamma derived from CpG-proBs enhanced IFN-gamma while dramatically reducing IL-21 production by Teffs. In keeping with the crucial pathogenic role played by IL-21 in T1D, adoptively transferred IFN-gamma-deficient CpG-proBs did not prevent T1D development. Additionally, CpG-proBs matured in vivo into diverse pancreatic and splenic suppressive FasL(high) B-cell subsets. CpG-proBs may become instrumental in cell therapy of autoimmune diseases either on their own or as graft complement in autologous stemcell transplantation

Domains

Other

Dates and versions

hal-00845005 , version 1 (16-07-2013)

Identifiers

Cite

R. Montandon, S. Korniotis, E. Layseca-Espinosa, C. Gras, J. Megret, et al.. Innate pro-B cell progenitors protect against type 1 diabetes by regulating autoimmune effector T cells.. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110, pp.E2199-E2208. ⟨10.1073/pnas.1222446110⟩. ⟨hal-00845005⟩

Collections

CNRS
36 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More