PMID- 35479094
OWN - NLM
STAT- MEDLINE
DCOM- 20220429
LR  - 20220716
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - CpG-Activated Regulatory B-Cell Progenitors Alleviate Murine 
      Graft-Versus-Host-Disease.
PG  - 790564
LID - 10.3389/fimmu.2022.790564 [doi]
LID - 790564
AB  - Development of Graft Versus Host Disease (GVHD) represents a major impediment in 
      allogeneic hematopoietic stem cell transplantation (HSCT). The observation that 
      the presence of bone marrow and circulating hematogones correlated with reduced 
      GVHD risks prompted us to evaluate whether B-cell progenitors, which provide 
      protection in various autoimmune disease models following activation with the 
      TLR-9 agonist CpG (CpG-proBs), could likewise reduce this allogeneic disorder. In 
      a murine model of GVHD that recapitulates an initial phase of acute GVHD followed 
      by a phase of chronic sclerodermatous GVHD, we found that CpG-proBs, adoptively 
      transferred during the initial phase of disease, reduced the diarrhea score and 
      mostly prevented cutaneous fibrosis. Progenitors migrated to the draining lymph 
      nodes and to the skin where they mainly differentiated into follicular B cells. 
      CpG activation and IFN-gamma expression were required for the protective effect, 
      which resulted in reduced CD4(+) T-cell-derived production of critical cytokines 
      such as TGF-beta, IL-13 and IL-21. Adoptive transfer of CpG-proBs increased the T 
      follicular regulatory to T follicular helper (Tfr/Tfh) ratio. Moreover, CpG-proBs 
      privileged the accumulation of IL-10-positive CD8(+) T cells, B cells and 
      dendritic cells in the skin. However, CpG-proBs did not improve survival. 
      Altogether, our findings support the notion that adoptively transferred CpG-proBs 
      exert immunomodulating effect that alleviates symptoms of GVHD but require 
      additional anti-inflammatory strategy to improve survival.
CI  - Copyright (c) 2022 Agbogan, Gastineau, Tejerina, Karray and Zavala.
FAU - Agbogan, Viviane A
AU  - Agbogan VA
AD  - Universite Paris Cite, INSERM U1151, CNRS UMR8152, Institut Necker Enfants 
      Malades (INEM), Paris, France.
FAU - Gastineau, Pauline
AU  - Gastineau P
AD  - Universite Paris Cite, INSERM U1151, CNRS UMR8152, Institut Necker Enfants 
      Malades (INEM), Paris, France.
FAU - Tejerina, Emmanuel
AU  - Tejerina E
AD  - Universite Paris Cite, INSERM U1151, CNRS UMR8152, Institut Necker Enfants 
      Malades (INEM), Paris, France.
FAU - Karray, Saoussen
AU  - Karray S
AD  - Universite Paris Cite, INSERM U976, Institut de Recherche Saint-Louis (IRSL), 
      Hopital Saint-Louis, Paris, France.
FAU - Zavala, Flora
AU  - Zavala F
AD  - Universite Paris Cite, INSERM U1151, CNRS UMR8152, Institut Necker Enfants 
      Malades (INEM), Paris, France.
LA  - eng
PT  - Journal Article
DEP - 20220411
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
SB  - IM
MH  - Animals
MH  - *B-Lymphocytes, Regulatory
MH  - CD8-Positive T-Lymphocytes
MH  - *Graft vs Host Disease/prevention & control
MH  - *Hematopoietic Stem Cell Transplantation/methods
MH  - Mice
MH  - Mice, Inbred C57BL
PMC - PMC9035844
OTO - NOTNLM
OT  - Bregs: regulatory B cells
OT  - CpG-proBs
OT  - allogeneic stem cell transplantation (allo-SCT)
OT  - cell therapy
OT  - fibrosis
OT  - graft-versus host disease
OT  - regulatory B-cell progenitors
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/29 06:00
MHDA- 2022/04/30 06:00
PMCR- 2022/01/01
CRDT- 2022/04/28 06:15
PHST- 2021/10/06 00:00 [received]
PHST- 2022/03/21 00:00 [accepted]
PHST- 2022/04/28 06:15 [entrez]
PHST- 2022/04/29 06:00 [pubmed]
PHST- 2022/04/30 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.790564 [doi]
PST - epublish
SO  - Front Immunol. 2022 Apr 11;13:790564. doi: 10.3389/fimmu.2022.790564. eCollection 
      2022.