G-CSF modulates innate and adaptive immunity via the ligand-receptor pathway of binding GCSFR in flounder (Paralichthys olivaceus)

Abstract

Granulocyte colony stimulating factor (G-CSF) has been shown in mammalia to activate a series of signal transduction systems and exert various biological effects, such as controlling the differentiation, proliferation, and survival of granulocytes, promoting the movement of hematopoietic stem cells from the bone marrow to the bloodstream, and triggering the development of T cells, dendritic cells, and immune tolerance in transplants. In this study, the mRNA of flounder G-CSF (PoG-CSF) and its receptor (PoGCSFR) were detected and widely expressed in all examined tissues with the highest expression in peritoneal cells. G-CSF⁺ and GCSFR⁺ cells were observed to be abundantly distributed in the leukocytes from the peritoneal cavity, followed by head kidney. PoG-CSF was detected in IgM⁺, CD4⁺, MHCII⁺ and CD83⁺ cells which indicated that flounder lymphocytes, dendritic cells and other MHCII positive cells may produce G-CSF protein. PoGCSFR was expressed in the MPO⁺ cells, suggesting that PoGCSFR is mainly expressed in flounder granulocytes. In addition, rPoG-CSF demonstrated a capacity to enhance the phagocytosis of peritoneal cells and HK leukocytes in vitro. In vivo, the percentage of IgM⁺, CD4⁺, MHCII⁺, CD83⁺ and GCSFR⁺ cells in the peritoneal cavity increased after rPoG-CSF i.p. stimulation. It seemed that rPoG-CSF promoted the migration of innate cells from the head kidney into the peritoneal cavity. Meanwhile, administration of rPoG-CSF increased the expression levels of the inflammatory cytokines. Finally, drawing of the interfaces of G-CSF and GCSFR showed the principal hydrogen-bonding linkages. This study suggests that G-CSF as a pleiotropic growth factor binding to GCSFR may be involved in the regulation of innate and adaptive responses.

Keywords: Fish; Granulocyte colony stimulating factor; Granulocyte colony stimulating factor receptor; Immune response.