Gm40600 promotes CD4+ T-cell responses by interacting with Ahnak

Immunology. 2021 Sep;164(1):190-206. doi: 10.1111/imm.13365. Epub 2021 Jun 2.

Abstract

It is important to characterize novel proteins involved in T- and B-cell responses. Our previous study demonstrated that a novel protein, Mus musculus Gm40600, reduced the proliferation of Mus musculus plasmablast (PB)-like SP 2/0 cells and B-cell responses induced in vitro by LPS. In the present study, we revealed that Gm40600 directly promoted CD4+ T-cell responses to indirectly up-regulate B-cell responses. Importantly, we found that CD4+ T-cell responses, including T-cell activation and differentiation and cytokine production, were increased in Gm40600 transgenic (Tg) mice and were reduced in Gm40600 knockout (KO) mice. Finally, we demonstrated that Gm40600 promoted the Ahnak-mediated calcium signalling pathway by interacting with Ahnak to maintain a cytoplasmic lateral location of Ahnak in CD4+ T cells. Collectively, our data suggest that Gm40600 promotes CD4+ T-cell activation to up-regulate the B-cell response via interacting with Ahnak to promote the calcium signalling pathway. The results suggest that targeting Gm40600 may be a means to control CD4+ T-cell-related diseases.

Keywords: Ahnak; B cells; CD4+ T cells; Gm40600; Th cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Calcium Signaling
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • Immunity, Humoral
  • Immunomodulation
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Leukemia Virus, Murine / genetics*
  • Lymphocyte Activation
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasm Proteins / metabolism*
  • RNA-Directed DNA Polymerase / genetics

Substances

  • Ahnak protein, mouse
  • Cytokines
  • Gm40600 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Neoplasm Proteins
  • RNA-Directed DNA Polymerase