Papers

Peer-reviewed
Feb, 2015

Anti-IL-12/23 p40 Antibody Attenuates Experimental Chronic Graft-versus-Host Disease via Suppression of IFN-gamma/IL-17-Producing Cells

JOURNAL OF IMMUNOLOGY
  • Sachiyo Okamoto
  • ,
  • Hideaki Fujiwara
  • ,
  • Hisakazu Nishimori
  • ,
  • Ken-ichi Matsuoka
  • ,
  • Nobuharu Fujii
  • ,
  • Eisei Kondo
  • ,
  • Takehiro Tanaka
  • ,
  • Akihiko Yoshimura
  • ,
  • Mitsune Tanimoto
  • ,
  • Yoshinobu Maeda

Volume
194
Number
3
First page
1357
Last page
1363
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.4049/jimmunol.1400973
Publisher
AMER ASSOC IMMUNOLOGISTS

Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity after allogeneic hematopoietic cell transplantation. Recently, in addition to Th2 cells, Th1 and Th17 cells have been shown to contribute to chronic GVHD progression. IL-12 induces Th1 cells and IL-23 plays a role in stabilizing and/or amplifying Th17 cells, as well as in inducing IFN-gamma/IL-17 double-producing cells. Because mAb targeting the p40 subunit common to both IL-12 and IL-23 can inhibit both IL-12R and IL-23R-mediated signaling, we investigated the effects of anti-p40 mAb on a well-defined chronic GVHD mice model. Treatment of anti-p40 mAb in allogeneic recipients significantly reduced the severity of clinical and pathological chronic GVHD. Intracellular staining revealed that IFN-gamma single-positive (IL-17(-)) and IFN-gamma/IL-17 double-positive cells were suppressed in anti-p40 mAb-treated allogeneic recipients compared with control recipients. The cytokine levels of IFN-gamma and IL-17 were also decreased in serum from anti-p40 mAb-treated allogeneic recipients. T-bet expression of donor IL-17(+) CD4(+) T cells was reduced significantly in anti-p40 mAb-treated recipients, and this reduction in T-bet expression was associated with IL-22 production by donor T cells. These results suggested that anti-p40 mAb attenuated chronic GVHD via suppression of IFN-gamma/IL-17-producing cells, and that targeting the IL-12/IL-23 pathway may represent a promising therapeutic strategy for preventing and treating chronic GVHD.

Link information
DOI
https://doi.org/10.4049/jimmunol.1400973
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000348134000055&DestApp=WOS_CPL
URL
http://www.scopus.com/inward/record.url?eid=2-s2.0-84921483083&partnerID=MN8TOARS
URL
http://orcid.org/0000-0003-0995-9405
ID information
  • DOI : 10.4049/jimmunol.1400973
  • ISSN : 0022-1767
  • eISSN : 1550-6606
  • ORCID - Put Code : 47323585
  • SCOPUS ID : 84921483083
  • Web of Science ID : WOS:000348134000055

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