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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01861

The fibrosis and immunological features of hypochlorous acid induced mouse model of systemic sclerosis

  • 1Xiangya Hospital, Central South University, China
  • 2Xiangya School of Medicine, Central South University, China
  • 3School of Life Science, Central South University, China

Fibrotic animal model is critical for the pathogenesis investigations and drug explorations in Systemic sclerosis (SSc).The bleomycin (BLM)-induced mouse model is the classical and most widely used fibrosis model. However, traditional subcutaneous injection of BLM does not cause diffuse skin lesions and rarely induces lung fibrosis or autoantibody production. Hypochlorous acid(HClO)-induced mice are a more representative model that have diffuse cutaneous lesions, lung fibrosis and renal involvement, along with the production of serum anti-DNA topoisomerase 1 autoantibodies. While the fibrosis and immunological features of this model are not fully elucidated. Here, we used different concentrations of HClO (1:55, 1:70, and 1:110 NaClO: KH2PO4, hereafter named HClO55, HClO70, and HClO110, respectively) and injected BALB/c mice subcutaneously for 6 weeks, and also used HClO110 for different time courses (4, 5 and 6 weeks). HE and Masson’s trichrome staining were used to observe the morphological changes. Immunohistochemistry or real-time PCR was used to detect inflammatory infiltrates, important fibrosis pathways and pro-inflammatory mediator expression. Flow cytometry was used to detect the alteration of immune cells in mouse spleen. Skin and lung fibrosis were most obvious in the HClO55 group. In the HClO110 group, dominant inflammatory infiltrates was found at 5 weeks, and significant fibrosis was found at 6 weeks. Then we explored the fibrosis and immunological profiles in the HClO110 (6 weeks) group.
Important fibrosis pathway proteins such as TGF-β, NF-κB, Smad3, p-Smad3, STAT3, and p-STAT3 were significantly elevated. Increased infiltration of CD4+T cells, CD8+T cells, CD20+B cells, and myofibroblasts was found both in skin and lung tissues. However, decreased CD4+T cells, CD8+T cells, monocytes and macrophages and increased CD19+B cells was found in the spleen tissues. The mRNA expression of fibrosis mediators such as IL-1β, IL-6, IL-17, IL-33, TNF-α, and CTGF was also upregulated. In conclusion, HClO induced fibrosis mouse model displayed systemic immune cell infiltrates, pro-inflammatory mediator release, vasculopathy and fibrosis, which better mimicked human SSc than BLM-induced mice.

Keywords: HClO-induced mice, Immune Cell Infiltration, Pro-inflammatory mediators, Fibrosis, systemic sclerosis

Received: 24 Apr 2019; Accepted: 23 Jul 2019.

Edited by:

DIMITRIOS P. BOGDANOS, University of Thessaly, Greece

Reviewed by:

Selvi Enrico, Siena University Hospital, Italy
Wioleta Marut, University Medical Center Utrecht, Netherlands  

Copyright: © 2019 Zhu, Wang, Meng, Tan, Chen, Du, Xie and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Honglin Zhu, Xiangya Hospital, Central South University, Changsha, China, honglinzhu@csu.edu.cn
Mx. Kangkai Wang, Xiangya School of Medicine, Central South University, Changsha, 410008, Hunan Province, China, Kangkaiwang@csu.edu.cn