4.8 Article

Nrf2 Participates in M2 Polarization by Trichinella spiralis to Alleviate TNBS-Induced Colitis in Mice

Journal

FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.698494

Keywords

Trichinella spiralis; macrophage; TNBS; colitis; Th2; Nrf2

Categories

Funding

  1. National Key Research and Development Program of China [2018YFC1602500, 2017YFC1601200]
  2. National Natural Science Foundation of China [31520103916, 31872467]
  3. Program for JLU Science and Technology Innovative Research Team [2017TD-32]

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This study revealed that Nrf2 is essential for M2 polarization induced by T. spiralis ES to alleviate colitis in mice. Adoptive transfer of ES-treated M2 decreased IFN-gamma levels and increased IL-4 and IL-10 levels in vivo, while ES-treated Nrf2 KO macrophages showed impaired ability to treat colitis with deficient elevation of IL-4 and IL-10 levels.
Trichinella spiralis induced alternative activated macrophages (M2), leading to protect against Crohn's disease, known as Th1 -related inflammation, which enhances oxidative stress in the host. However, the relationship of oxidative stress and T. spiralis -mediated immune response is still unknown. In our study, we showed that nuclear factor erythroid 2-related factor-2 (Nrf2), a key transcription factor in antioxidant, participated in M2 polarization induced by T. spiralis muscle larval excretory/secretory (ES) products in vitro. ES -treated M2 were injected intravenously after TNBS challenge and we demonstrated that ES-M could alleviate the severity of the colitis in mice. Adoptive transfer of ES -treated M2 decreased the level of IFN-gamma and increased the levels of IL-4 and IL-10 in vivo. However, the capacity of ES -treated Nrf2 KO macrophages to treat colitis was dramatically impaired. ES -treated Nrf2 KO macrophages was insufficient to result in the elevated levels of IL-4 and IL-10. These findings indicate that Nrf2 was required for M2 polarization induced by T. spiralis ES to alleviate colitis in mice.

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