Investigations on the Relations of Rheumatoid Arthritis and Rheumatic Fever to Allergy

Abstract

Transgenic zebrafish that express fluorophores under the control of <i>mpeg1.1</i> (<i>mpeg1</i>) and <i>csf1ra</i> (<i>c-fms</i>) promoters have been widely used to study the dynamics and functions of mononuclear phagocytes (MNPs) in larval zebrafish, unveiling crucial roles for these innate immune cells in many processes, including tissue repair. Adult zebrafish are also being increasingly used as a model organism for such studies because of their regenerative capacity and presence of innate and adaptive immune cells. For example, recent investigations highlight roles of MNPs in the regulation of diverse cellular processes during heart regeneration, including scarring, cardiomyocyte proliferation, and neovascularization. However, transgenic lines that stratify MNP subpopulations (monocytes, macrophages, and dendritic cells) are not yet available, preventing functional analysis of these populations. In an attempt to better segregate cardiac MNPs, we assessed the coexpression of <i>mpeg1.1</i> and <i>csf1ra</i> reporter transgenes in adult zebrafish hearts. Unexpectedly, this also identified a discrete population of <i>mpeg1.1</i>⁺<i>csf1ra</i>⁻ lymphoid-like cells, which respond to cardiac cryoinjury in a different temporal pattern to <i>mpeg1.1</i>⁺ MNPs. <i>mpeg1.1</i>⁺ lymphoid cells were also abundant in the skin, spleen, and blood, and their frequency was unaffected in the hearts of <i>csf1ra^j4e1/j4e1</i> mutant zebrafish, which display deficiencies in MNP populations. Flow cytometry, imaging, and cytological and gene expression analyses collectively indicate that these cells comprise a mixed population of B cells and NK-like cells. Our study therefore highlights the need to identify novel MNP lineage markers but also suggests undetermined roles of B cells and NK-like cells in cardiac homeostasis and repair in adult zebrafish.