2. Academic Validation
  3. Regulatory T cells were recruited by CCL3 to promote cryo-injured muscle repair

Regulatory T cells were recruited by CCL3 to promote cryo-injured muscle repair

  • Immunol Lett. 2018 Dec;204:29-37. doi: 10.1016/j.imlet.2018.10.004.
Chaoqi Zhang 1,  Yamin Qiao 2,  Lan Huang 3,  Feng Li 4,  Zhen Zhang 3,  Yu Ping 3,  Zhibo Shen 1,  Jingyao Lian 3,  Feng Li 3,  Lixuan Zhao 5,  Yi Zhang 6
Affiliations

Affiliations

  • 1 Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China; Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 2 Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 3 Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 4 Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 5 Department of Cardiac surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 6 Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China; Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China; School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China; Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan 450052, China. Electronic address: yizhang@zzu.edu.cn.
PMID: 30321562 DOI: 10.1016/j.imlet.2018.10.004
Abstract

Skeletal muscle injury is a common symptom in daily life. After injury, a distinct population of regulatory T cells (Tregs) will infiltrate skeletal muscle in acute and chronic injury sites. However, the mechanism by which Tregs rapidly accumulate to the site of acute injury remains unclear. BALB/c mice were used to establish a cryo-injured model. Percentage of Tregs in the normal and cryo-injured tissues was detected on different days by flow cytometry. Then, the major factors that contribute to the repair of skeletal muscle by Tregs and the chemokines associated with the chemotaxis of Tregs in the paired muscle were analyzed by qRT-PCR. Finally, Tregs were sorted out by Magnetic Beads and the transwell analysis was performed in vitro. Compared to the normal muscle, the proportion of Tregs was dramatically-increased in the cryo-injured muscle on day 4. These Tregs produced high level of repair related factors such as Amphiregulin (Areg), IL-10 and TGF-β in the cryo-injured muscle. In addition, we found that CCL3, CCL4, CCL5 were the main chemokines that highly expressed in the injured skeletal muscle compared to the normal skeletal muscle. Simultaneously, their receptors CCR1 and CCR5 were highly expressed on Tregs in cryo-injured muscle compared with the normal muscle. Transwell analysis showed CCL3 can significantly chemotize Tregs and the antibody of CCR1 could reverse the chemotaxis in vitro. These results suggest that Tregs in the cryo-injured muscle play a pivotal role that can promote the regeneration of skeletal muscle and CCL3 may serve as the key chemokine to recruit Tregs to the injury sites.

Keywords

CCL3; CCR1; CCR5; Repair; Skeletal muscle; Tregs.

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