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B Lymphocyte Chemoattractant (CXCL13) Is an Indicator of Acute Gastrointestinal GVHD in Murine Model

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Abstract

Gastrointestinal acute graft-vs.-host disease (GI aGVHD) remains a significant obstacle to the success of allogeneic hematopoietic cell transplantation and is a major cause of morbidity and mortality. In addition, GI aGVHD is often clinically indistinguishable from other causes of GI dysfunction such as conditioning regimen toxicity, infections, or medications, which complicates the diagnosis. Thus, specific biomarkers are needed to help improve diagnosis and obtain a deeper understanding of the cytokine changes in GI aGVHD. An MHC-mismatched model of aGVHD was established by transplanting 1 × 107 bone marrow nuclear cells and 3 × 107 spleen cells from C57/Bl6 mice or from BALB/c mice into lethally irradiated BALB/c recipients. The mice in the allogeneic transplantation group were intraperitoneally treated with 20 mg kg−1 day−1 cyclosporin A after aGVHD developed. Five micrograms of lipopolysaccharide were administered intraperitoneally daily to syngeneic recipients at day 11 to imitate infection; the same volume of phosphate-buffered saline was administered to control mice. The mice were killed at the indicated time points. Forty molecules derived from the GI tract were screened cytokine array. The data demonstrated that the expression of B lymphocyte chemoattractant (CXCL13) was increased by ~10-, 12-, and 16-fold upon the occurrence of aGVHD compared with infection, aGVHD after treatment, and the syngeneic control group, respectively. Thus, the elevation of BLC (CXCL13) is an indicator of acute GI GVHD.

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Acknowledgments

This work was supported by the Zhejiang Provincial Natural Science Foundation of China under Grant Nos. LY13H080003 and LY12H08002 and Wenzhou Municipal Sci-Tech Bureau’s program under Grant No. Y20120045. We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

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Authors and Affiliations

  1. Hematopoietic Stem Cell Transplantation Center, Institute of Hematology and Blood Diseases Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, 300020, China

    Yigeng Cao, Erlie Jiang & Mingzhe Han

  2. Wenzhou Medical University, Wenzhou, Zhejiang, 325002, China

    Xiaoyi Qin & Na Wang

  3. Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Nan Bai Xiang Street, Ouhai District, Wenzhou, Zhejiang, 325002, China

    Yongyong Ma, Bin Liang, Kang Yu & Haige Ye

  4. Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Nan Bai Xiang Street, Ouhai District, Wenzhou, Zhejiang, 325002, China

    Kaiyan Yang

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  1. Yigeng Cao
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Correspondence to Haige Ye.

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This work was supported by Zhejiang Provincial Natural Science Foundation of China (LY13H080003 to Y.H.G and Y12H080012 to L.B).

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Yigeng Cao, Xiaoyi Qin, and Na Wang contributed equally to this work.

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Cao, Y., Qin, X., Wang, N. et al. B Lymphocyte Chemoattractant (CXCL13) Is an Indicator of Acute Gastrointestinal GVHD in Murine Model. Inflammation 40, 1678–1687 (2017). https://doi.org/10.1007/s10753-017-0609-2

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