Rainbow trout CK9, a CCL25-like ancient chemokine that attracts and regulates B cells and macrophages, the main antigen presenting cells in fish.

Carolina Aquilino,Beatriz Abos,Christopher J Secombes,Tiehui Wang,Aitor G Granja,David Parra,Carolina Tafalla,Rosario Castro

doi:10.18632/oncotarget.8163

Carolina Aquilino, Beatriz Abos + Show 6 more

Open Access

https://doi.org/10.18632/oncotarget.8163

Copy DOI

Abstract

CK9 is a rainbow trout (Oncorhynchus mykiss) CC chemokine phylogenetically related to mammalian CCL25. Although CK9 is known to be transcriptionally regulated in response to inflammation particularly in mucosal tissues, its functionality has never been revealed. In the current work, we have demonstrated that CK9 is chemoattractant for antigen presenting cells (APCs) expressing major histocompatibility complex class II (MHC II) on the cell surface. Among these APCs, CK9 has a strong chemotactic capacity for both B cells (IgM+ and IgT+) and macrophages. Along with its chemotactic capacities, CK9 modulated the MHC II turnover of B lymphocytes and up-regulated the phagocytic capacity of both IgM+ cells and macrophages. Although CK9 had no lymphoproliferative effects, it increased the survival of IgT+ lymphocytes. Furthermore, we have established that the chemoattractant capacity of CK9 is strongly increased after pre-incubation of leukocytes with a T-independent antigen, whereas B cell receptor (BCR) cross-linking strongly abrogated their capacity to migrate to CK9, indicating that CK9 preferentially attracts B cells at the steady state or under BCR-independent stimulation. These results point to CK9 being a key regulator of B lymphocyte trafficking in rainbow trout, able to modulate innate functions of teleost B lymphocytes and macrophages.

Highlights

Chemokines or chemotactic cytokines are a family of cytokines that regulate immune cell migration under both inflammatory and normal physiological conditions
We have established the chemoattractant potential of CK9, an ancient chemokine with close homology to mammalian CCL25, towards trout MHC major histocompatibility complex class II monocyte chemotactic protein (MCP) (II)+ antigen presenting cells (APCs), including B lymphocytes and macrophages, and established its potential to regulate specific immune functions in the different recruited cell types
CCL25 has been shown to promote the differentiation of monocytes to macrophages [25] and likewise, we have observed an activation of macrophages in response to CK9, on their phagocytic and respiratory burst activity, which should increase their antigen presenting and microbicidal potential

Summary

Introduction

Chemokines or chemotactic cytokines are a family of cytokines that regulate immune cell migration under both inflammatory and normal physiological conditions. In 2007, Peatman and Liu established seven large groups of fish CC chemokines through an extensive phylogenetic analysis using CC chemokine sequences from rainbow trout (Oncorhynchus mykiss), Atlantic salmon (Salmo salar), channel catfish (Ictalurus punctatus) and zebrafish (Danio rerio) along with mammalian CC chemokines [5]. These groups were named based on their mammalian membership as the CCL19/21/25 group, the CCL20 www.impactjournals.com/oncotarget group, the CCL27/28 group, the CCL17/22 group, the macrophage inflammatory protein (MIP) group, the monocyte chemotactic protein (MCP) group and a fishspecific group. The CCL19 subclade in the CCL19/21/25 group is well established and constitutes an independent gene [5]

Methods

Results

Conclusion