Key Points
CXCR4a and CXCR4b prefer to bind LPS and SDF-1 in teleosts, respectively.
CXCR4b inhibits HSPC proliferation in ayu by regulating ROS levels.
CXCR4a+ HSPCs are prone to differentiate into myeloid cells in ayu.
Abstract
Hematopoietic stem/progenitor cells (HSPCs) generate the entire repertoire of immune cells in vertebrates and play a crucial role during infection. Although two copies of CXC motif chemokine receptor 4 (CXCR4) genes are generally identified in teleosts, the function of teleost CXCR4 genes in HSPCs is less known. In this study, we identified two CXCR4 genes from a teleost, ayu (Plecoglossus altivelis), named PaCXCR4a and PaCXCR4b. PaCXCR4b was constitutively expressed in ayu HSPCs, whereas PaCXCR4a was induced by LPS treatment. The stromal-derived factor-1–binding activity of CXCR4b was significantly higher than that of CXCR4a, whereas the LPS-binding activity of CXCR4a was significantly higher than that of CXCR4b in the teleosts ayu, large yellow croaker (Larimichthys crocea), and tiger puffer (Takifugu rubripes). CXCR4a+ HSPCs were mobilized into blood by LPS, whereas CXCR4b+ HSPCs were mobilized by leukocyte cell–derived chemotaxin-2. PaSDF-1 and PaCXCR4b, but not PaCXCR4a, inhibited HSPC proliferation by regulating reactive oxygen species levels. Compared with PaCXCR4b+ HSPCs, PaCXCR4a+ HSPCs preferentially differentiated into myeloid cells in ayu by maintaining high stem cell leukemia expression. These data suggest that the two copies of CXCR4s achieve a division of labor in the regulation of teleost HSPC homeostasis, supporting the concept that subfunctionalization after gene duplication in teleosts may stabilize the immune system.
Footnotes
This work was supported by the Program for the Natural Science Foundation of China (31972821; 31772876; 41776151), the Zhejiang Provincial Natural Science Foundation of China (LR18C040001; LZ18C190001), the Scientific Innovation Team Project of Ningbo (2015C110018) and the K.C. Wong Magna Fund in Ningbo University.
The sequences presented in this article have been submitted to GenBank (https://www.ncbi.nlm.nih.gov/genbank/) under accession numbers MN148390, MN148391, MN148393, MN158722, MN158723, MN158724, MN156535, and MN156536, MN628572, MN628573.
The online version of this article contains supplemental material.
- Received September 10, 2019.
- Accepted December 11, 2019.
- Copyright © 2020 by The American Association of Immunologists, Inc.