In the vast, watery world of fish, scientists have discovered a cellular mechanism that could reshape our understanding of inflammatory diseases and their treatments. A team led by Jie Wang from the National Key Laboratory of Agricultural Microbiology at Huazhong Agricultural University has identified a unique subset of immune cells in fish that bear striking similarities to regulatory B cells (Bregs) found in mammals. These findings, published in Cell Communication and Signaling, open new avenues for exploring the evolutionary origins of immune regulation and could have significant implications for human health and the aquaculture industry.
Regulatory B cells are known for their immunosuppressive properties, playing a crucial role in controlling inflammatory diseases by producing interleukin-10 (IL-10). While Bregs have been studied extensively in mammals, their existence in non-mammalian vertebrates remained unclear until now. Wang’s team focused on the grass carp, a cold-blooded vertebrate, to uncover the differentiation mechanism and functional profiles of teleost CD25L+ Bregs.
The researchers identified a unique IgM+CD25L+ B cell subset in the grass carp, characterized by its ability to produce IL-10 and IL-12p35. “We found that these cells act similarly to mammalian Bregs, exerting immunosuppressive functions on effector T cells and neutrophils,” Wang explained. The team demonstrated that IL-35 stimulation induced the differentiation of CD25L− B cells into CD25L+ B cells, promoting the production of IL-35 and IL-10 via STAT3 activation.
The implications of this discovery are far-reaching. Understanding the evolutionary origins of Bregs could provide insights into the development of new therapies for inflammatory diseases in humans. Moreover, this research has significant implications for the aquaculture industry, which faces substantial challenges from infectious diseases and inflammatory conditions.
In an inflammatory bowel disease (IBD) model induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS), the team found that the frequency of Bregs and IL-10 levels increased significantly during IBD remission. Adoptive transfer of Bregs could prevent IBD development and contribute to intestinal tissue repair. This suggests that manipulating Breg activity could be a viable strategy for managing inflammatory diseases in both fish and humans.
The commercial impacts for the energy sector are indirect but significant. Aquaculture is a growing industry that requires sustainable and efficient practices to meet the increasing demand for seafood. Infectious diseases and inflammatory conditions can decimate fish populations, leading to substantial economic losses. By understanding and harnessing the immune mechanisms of fish, the aquaculture industry can develop more resilient and productive farming practices, ultimately contributing to a more sustainable food supply.
This research also highlights the importance of studying non-mammalian models to gain a deeper understanding of immune regulation. “Fish have evolved Bregs with specialized anti-inflammatory functions, providing evolutionary insights into the phylogenetic origin and functional conservation of Bregs from fish to mammals,” Wang noted. This evolutionary perspective could lead to the development of novel therapies and interventions for a wide range of inflammatory diseases.
As the field of immunology continues to evolve, the discovery of Bregs in fish offers a fresh perspective on the origins and functions of these critical immune cells. By bridging the gap between fish and mammalian immunology, researchers can uncover new strategies for managing inflammatory diseases and improving the sustainability of the aquaculture industry. The findings published in Cell Communication and Signaling, translated as Cell Signaling and Communication, represent a significant step forward in our understanding of immune regulation and its evolutionary roots.