The skin of most vertebrates is infiltrated by immune cells, but little is known about the origin and behavior of these cells. Now researchers find that certain immune cells in fish skin respond much like the immune cells found in fish intestine, say findings detailed in this week’s Proceedings of the National Academy of Sciences.
Mucus membranes such as those lining the gut serve as a first line of defense against microbes in all vertebrates. In contrast, the skin of early vertebrates such as fish, unlike that of more recently evolved vertebrates that colonized the land, also behaves like a mucus membrane, harboring abundant mucus-producing cells.
The skin of most vertebrates contains diffuse lymphoid tissue possessing immune cells such as B cells. The oldest living bony vertebrates with this kind of skin-associated lymphoid tissue are teleost fish.
Intriguingly, teleost skin-associated lymphoid tissue structurally resembles gut-associated lymphoid tissue (GALT), and similarly is in intimate contact with a large, diverse community of microbes. As such, evolutionary immunologist Oriol Sunyer at the University of Pennsylvania in Philadelphia and his colleagues reasoned that teleost skin and GALT experienced similar evolutionary forces and would therefore respond in similar ways to infection. After analyzing the skin of the rainbow trout, the researchers confirmed the B cell content and antibody responses of fish skin strikingly resemble those of their gut. “One could consider teleost fish as an open gut swimming,” Sunyer says.
Three classes of antibodies have been discovered in teleosts — IgM, IgD and IgT (also known as IgZ in certain species). Sunyer and his colleagues had previously found that IgT played a role in fish gut mucosal immunity, and now they show that resident IgT-producing B cells in the fish epidermis produce the majority
of antibody that coats microbes associated with the skin.
Mammals also possess skin-associated lymphoid tissue (SALT), but it bears little resemblance to its teleost counterpart. Instead, the scientists found teleost skin resembled the mucous membrane-associated lymphoid tissue of mammals. This work suggests analyzing teleost skin might shed light on the general principles underlying mammalian immunity in mucus membranes.
For example, one question this work raises is “are there any conserved immune mechanisms in immune responses elicited by the fish and mammalian skin?” Sunyer says. “Some of the bacterial microbiota in mammalian skin are coated by IgA — is that IgA stimulated in a similar manner as the IgT coating the fish skin microbiota?”
In addition, from a more practical perspective, “our studies are very relevant to improving the health of farmed fish,” Sunyer says. “It is well known that fish skin is a major portal for pathogens for which vaccines are still unavailable. Thus, the knowledge derived from our findings will be critical for the future evaluation and rational design of fish vaccines that stimulate mucosal immune responses in the skin.”