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MANF regulates splenic macrophage differentiation in mice

Chao Hou1, Dong Wang1, Xiang Li1

  • 1School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, Anhui, China; Biopharmaceutical Research Institute, Anhui Medical University, Hefei 230032, Anhui, China.

Immunology Letters
|June 22, 2019
PubMed

Insights

Mesencephalic astrocyte-derived neurotrophic factor (MANF) regulates splenic immune cells. MANF knockout in macrophages increases M1 macrophages and, during liver fibrosis, M2 macrophages and plasma cells, impacting spleen function.

Area of Science:

  • Immunology
  • Cell Biology
  • Neuroscience

Background:

  • Splenic immune cells, particularly macrophages, are crucial in various diseases.
  • Mesencephalic astrocyte-derived neurotrophic factor (MANF) has known anti-inflammatory effects.
  • The role of MANF in splenic immune cell regulation remains unclear.

Purpose of the Study:

  • To investigate the function of MANF in splenic immune cells.
  • To determine MANF's effect on macrophage differentiation in the spleen.
  • To assess MANF's impact on splenic immune responses during hepatic fibrosis.

Main Methods:

  • Generation of mono-macrophage-specific MANF knockout (Mø MANF-/-) mice.
  • Induction of carbon tetrachloride (CCl4)-mediated hepatic fibrosis.
  • Analysis of splenic immune cell populations (macrophages, T cells, B cells, plasma cells) via flow cytometry and immunohistochemistry.
  • Measurement of serum and splenic TGF-β1 levels.

Main Results:

  • Mø MANF-/- mice exhibited increased splenic M1 macrophages under normal conditions.
  • In a model of hepatic fibrosis, Mø MANF-/- mice showed elevated splenic M2 macrophages and CD138+ plasma cells.
  • Serum and splenic TGF-β1 levels were increased in Mø MANF-/- mice with hepatic fibrosis.
  • MANF deficiency did not alter splenic T and B cell numbers in either normal or fibrotic states.

Conclusions:

  • MANF plays a distinct regulatory role in splenic immune cells, particularly macrophages.
  • MANF influences the differentiation of splenic macrophages.
  • MANF's regulation of splenic immunity may have significant implications for spleen physiology and pathology.
Keywords:
Hepatic fibrosisM1/M2 macrophage differentiationMesencephalic astrocyte-derived neurotrophic factorSpleen

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