ER stress-inducible protein MANF selectively expresses in human spleen

Hum Immunol. 2015 Nov;76(11):823-30. doi: 10.1016/j.humimm.2015.09.043. Epub 2015 Sep 30.

Abstract

Mesencephalic astrocyte-derived neurotrophic factor (MANF; also known as arginine-rich, mutated in early tumors; ARMET), is an ER stress-inducible protein, and widely expressed in mammalian tissues. In this study, we are interested in the profile of MANF expression in human splenocytes. Three patients with spleen trauma were enrolled in this study. Immunohistochemistry and immunofluorescence were used to detect MANF expression in the four types of cells, including T cells, B cells, plasma cells, and macrophages in spleens by using the specific antibodies of anti-CD3, anti-CD20, anti-CD138, and anti-CD68, respectively. We found that MANF-positive cells extensively distributed in the red pulp and marginal-zone of spleen, and MANF was almost localized in the cytoplasm of splenocytes. Double immunofluorescent staining results showed that MANF localized mainly in the plasma cells and macrophages, but not in T and B cells. Meanwhile, we found that some MANF-positive cells expressed ER stress-related proteins, including ATF6, XBP1s, BiP, and CHOP. These results suggest that the selective expression of MANF in splenocytes may be involved in plasma cell differentiation and immune regulation.

Keywords: Endoplasmic reticulum stress; MANF; Plasma cells; Spleen; Unfolded protein response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Endoplasmic Reticulum Stress / genetics*
  • Gene Expression*
  • Humans
  • Immunohistochemistry
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Nerve Growth Factors / genetics*
  • Nerve Growth Factors / metabolism
  • Organ Specificity / genetics
  • Plasma Cells / immunology
  • Plasma Cells / metabolism
  • Protein Transport
  • Spleen / immunology*
  • Spleen / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • MANF protein, human
  • Nerve Growth Factors