Published 6 issues per year
ISSN Print: 1040-8401
ISSN Online: 2162-6472
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Role of IL-26+CD26+CD4 T Cells in Pulmonary Chronic Graft-Versus-Host Disease and Treatment with Caveolin-1-Ig Fc Conjugate
ABSTRACT
Obliterative bronchiolitis is the primary noninfectious pulmonary complication after allogeneic hematopoietic cell transplantation and the only pathognomonic manifestation of pulmonary chronic graft-versus-host disease (cGVHD). In our recent study, we identified a novel effect of IL-26, which is absent in rodents, on transplant related-obliterative bronchiolitis. Sublethally irradiated NOD/Shi-scidIL2rγnull mice transplanted with human umbilical cord blood gradually exhibited obliterative bronchiolitis with increased collagen deposition and predominant infiltration with human IL-26+CD26+CD4 T cells. Moreover, we showed that IL-26 increased collagen synthesis in fibroblasts in vitro and that collagen contents were increased in a murine GVHD model using IL26 transgenic mice. In vitro analysis demonstrated a significant increase in IL-26 production by CD4 T cells following CD26 costimulation, while immunoglobulin Fc domain fused with the N-terminal of caveolin-1, the ligand for CD26, (Cav-Ig) effectively inhibited production of IL-26. Administration of Cav-Ig before or after onset of GVHD impeded the development of clinical and histologic features of GVHD without interrupting engraftment of donor-derived human cells, with preservation of the graft-versus-leukemia effect. We concluded that cGVHD of the lungs is caused in part by IL-26+CD26+CD4 T cells, and that treatment with Cav-Ig could be beneficial for cGVHD prevention and therapy.
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Hatano Ryo, Itoh Takumi, Otsuka Haruna, Okamoto Sayo, Komiya Eriko, Iwata Satoshi, Aune Thomas M., Dang Nam H., Kuwahara-Arai Kyoko, Ohnuma Kei, Morimoto Chikao, Characterization of novel anti-IL-26 neutralizing monoclonal antibodies for the treatment of inflammatory diseases including psoriasis, mAbs, 11, 8, 2019. Crossref
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Larochette Vincent, Miot Charline, Poli Caroline, Beaumont Elodie, Roingeard Philippe, Fickenscher Helmut, Jeannin Pascale, Delneste Yves, IL-26, a Cytokine With Roles in Extracellular DNA-Induced Inflammation and Microbial Defense, Frontiers in Immunology, 10, 2019. Crossref
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Itoh Takumi, Hatano Ryo, Horimoto Yoshiya, Yamada Taketo, Song Dan, Otsuka Haruna, Shirakawa Yuki, Mastuoka Shuji, Iwao Noriaki, Aune Thomas M., Dang Nam H., Kaneko Yutaro, Okumura Ko, Morimoto Chikao, Ohnuma Kei, IL-26 mediates epidermal growth factor receptor-tyrosine kinase inhibitor resistance through endoplasmic reticulum stress signaling pathway in triple-negative breast cancer cells, Cell Death & Disease, 12, 6, 2021. Crossref