Role of transcription factor c⁃Maf in macrophage polarization and memory T cell activation induced by BCG immunization

CAO Yige; TIAN Qing; SUN Sujuan; ZHANG Wenwen; LIU Min; LUO Fengling

doi:10.14188/j.1671-8852.2024.0724

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Role of transcription factor c⁃Maf in macrophage polarization and memory T cell activation induced by BCG immunization

更新时间：2026-11-05

- Role of transcription factor c⁃Maf in macrophage polarization and memory T cell activation induced by BCG immunization
- Medical Journal of Wuhan University Vol. 46, Issue 5, Pages: 583-594(2025)
- 作者机构：
  
  武汉大学泰康医学院（基础医学院）免疫学系湖北武汉 430071
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0724
  CLC： R378.911
- Received：23 September 2024，
  
  Published：25 May 2025
- 稿件说明：
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曹艺格,田晴,孙素娟等.转录因子c⁃Maf在卡介苗免疫后巨噬细胞极化和记忆T细胞活化中的作用[J].武汉大学学报（医学版）,2025,46(05):583-594.

CAO Yige,TIAN Qing,SUN Sujuan,et al.Role of transcription factor c⁃Maf in macrophage polarization and memory T cell activation induced by BCG immunization[J].Medical Journal of Wuhan University,2025,46(05):583-594.
曹艺格,田晴,孙素娟等.转录因子c⁃Maf在卡介苗免疫后巨噬细胞极化和记忆T细胞活化中的作用[J].武汉大学学报（医学版）,2025,46(05):583-594. DOI： 10.14188/j.1671-8852.2024.0724.

CAO Yige,TIAN Qing,SUN Sujuan,et al.Role of transcription factor c⁃Maf in macrophage polarization and memory T cell activation induced by BCG immunization[J].Medical Journal of Wuhan University,2025,46(05):583-594. DOI： 10.14188/j.1671-8852.2024.0724.

摘要

目的

探究转录因子c⁃Maf对卡介苗免疫中巨噬细胞极化和记忆T细胞活化的作用。

方法

用卡介苗体外刺激小鼠RAW264.7巨噬细胞、小鼠骨髓源性巨噬细胞（BMDMs）和经诱导的人单核细胞来源巨噬细胞THP⁃1，用RT⁃qPCR和Western Blot法检测卡介苗对巨噬细胞极化的影响；构建c⁃Maf过表达和敲低的RAW264.7巨噬细胞，用RT⁃qPCR、Western Blot、ELISA法和流式细胞术检测卡介苗对巨噬细胞极化的影响是否受转录因子c⁃Maf的调控；最后用卡介苗免疫野生型C57BL/6小鼠和巨噬细胞c⁃Maf条件性敲除的C57BL/6小鼠，30 d后用流式细胞术检测小鼠脾脏和肺脏中记忆T细胞的生成以及CD4

T细胞产生的细胞因子情况。

结果

体外实验显示，卡介苗诱导巨噬细胞呈现M1/M2混合表型。RAW264.7细胞中c⁃Maf的过表达促进了巨噬细胞向M2抗炎表型转变，而c⁃Maf的敲低则有利于M1促炎表型的转变。体内实验表明，巨噬细胞中c⁃Maf的定向敲除增加了卡介苗免疫后脾脏和肺脏中效应性记忆T细胞(T

)的比例，同时CD4

T细胞产生的促炎细胞因子水平升高。

结论

转录因子c⁃Maf在调节巨噬细胞M1和M2极化之间的平衡中起着至关重要的作用，并最终影响卡介苗诱导的适应性免疫反应的疗效，这为寻找抗结核新靶点拓宽了思路。

Abstract

Objective

To explore the role of transcription factor c⁃Maf in macrophage polarization and memory T cell activation induced by Bacillus Calmette⁃Guérin (BCG) immunization.

Methods

Mouse RAW264.7 macrophages

mouse bone marrow⁃derived macrophages (BMDMs)

and human monocyte⁃derived macrophages THP⁃1 were stimulated with BCG

in vitro

and the effects of BCG on macrophage polarization were detected by RT⁃qPCR and Western Blot. Then we constructed RAW264.7 macrophages with overexpression or knockdown of c⁃Maf

and detected whether the effect of BCG on macrophage polarization was regulated by the transcription factor c⁃Maf by RT⁃qPCR

Western Blot

ELISA

and flow cytometry assays. Finally

wild⁃type C57BL/6 mice and macrophage c⁃Maf conditional knockout mice were injected with BCG subcutaneously

the generation of memory T cells in the spleen and lung and the cytokines produced by CD4

T cells were detected by flow cytometry 30 days later.

Results

In vitro

experiments demonstrated that BCG⁃stimulated macrophages showed a mixed M1/M2 phenotype. Overexpression of c⁃Maf in RAW264.7 cells promoted the transformation of the M2 anti⁃inflammatory phenotype

while knockdown of c⁃Maf facilitated the transformation of the M1 pro⁃inflammatory phenotype.

In vivo

experiments showed that c⁃Maf conditional knockout in macrophages increased the proportion of effector memory T cells (T

) in the spleen and lung after BCG immunization

and the level of pro⁃inflammatory cytokines produced by CD4

T cells also increased.

Conclusion

Transcription factor c⁃Maf plays a crucial role in modulating the balance between M1 and M2 macrophage polarization and influences the efficacy of BCG⁃induced adaptive immune responses

thus providing new insights into finding targets against tuberculosis.

关键词

Keywords

references

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