Why A Shark's Pancreas Could Rewrite Immunology

Forbes

11-07-2025

This discovery adds a new chapter to our understanding of how the immune system evolved in jawed ... More vertebrates, especially in species that don't have lymph nodes like mammals do.
When we think of the pancreas, we think digestion, not defense. But in the nurse shark, that assumption has just been flipped on its head. New research reveals that this organ, tucked behind the stomach, doesn't just make enzymes and hormones — it's also an unexpected site of sophisticated immune activity.
Until now, the spleen was thought to be the only secondary lymphoid organ (SLO) in cartilaginous fish like sharks, rays, and skates. SLOs are critical zones where immune cells meet up, exchange information, and coordinate defenses against pathogens. In mammals, we have the spleen, lymph nodes, and gut-associated lymphoid tissue. But sharks don't have lymph nodes, and their gut-associated tissues don't show the same level of organization. So how do they coordinate immune responses? This study suggests the answer lies in a distributed network of immune-active tissues including the pancreas.
This wasn't discovered easily. Researchers acquired juvenile nurse sharks (Ginglymostoma cirratum) from the coastal waters around Florida and housed them in controlled, artificial seawater tanks to ensure they were healthy and acclimated before any testing. Some of these sharks were then immunized, meaning they were exposed to foreign proteins like phycoerythrin (a fluorescent protein often used in lab studies) or the SARS-CoV-2 spike protein to simulate an infection. These antigens were delivered either under the skin or intravenously, sometimes multiple times over the course of weeks. A few sharks were left unimmunized to serve as healthy controls. After the immunization period, the sharks were humanely euthanized and their organs, including the pancreas and spleen, were collected for analysis. The scientists used a technique called RNAscope fluorescence in situ hybridization; this method allowed them to visualize the location of specific RNA molecules within tissue sections. This was also paired with immunofluorescence microscopy, which uses antibodies linked to fluorescent dyes to tag specific proteins or cells. Together, these tools let researchers map out which immune cells were where, what genes they were expressing, and whether they were actively responding to the immunization.
Juvenile nurse shark resting under a rock ledge. (Photo by Wild Horizons/Universal Images Group via ... More Getty Images)
Traditionally we think of the pancreas as playing two key roles: making enzymes that help digest food and producing hormones like insulin to regulate blood sugar. But in nurse sharks, researchers found that the pancreas contains structured clusters of immune cells called B cell follicles. These are not scattered randomly, but are well-organized and sit apart from the parts of the pancreas that handle digestion or hormone production. Even more striking is how these B cell follicles behave. They mirror what's found in the spleen, which has long been recognized as a major player in immune defense. Like in the spleen, these pancreatic follicles hold onto intact pieces of pathogens (called antigens) and use them to help select the right B cells to fight off infection. After being exposed to a new antigen, such as during an experimental immunization, the nurse shark's pancreas actually began producing targeted antibodies, specific to that antigen.
These pancreatic B cell follicles weren't just found in immunized sharks. They were also present in healthy, unimmunized ones, showing that these structures aren't created by artificial stimulation. They are a normal part of nurse shark anatomy. This means the pancreas has been playing an immune role all along… we just hadn't looked closely enough. But it's not just B cells! The researchers also found clusters of T cells in the pancreas, including a population enriched in transcripts for TCR-γ, AID, and Ki67, suggesting active proliferation and somatic hypermutation. This is a process usually associated with fine-tuning immune cell receptors to better recognize pathogens. What's particularly curious is that these T cells likely don't rely on the major histocompatibility complex (MHC) for antigen recognition, hinting that they might behave like mammalian γδ T cells. In mammals, these types of cells are known for rapid responses at mucosal surfaces, where they help protect against infections in places like the gut and lungs.
So why would the pancreas be involved in this? One theory is that it provides a shortcut. The antibodies generated there could be funneled directly into the spiral valve (a structure in the shark's intestine) through the pancreatic duct. This would offer quick, local protection in a microbe-rich environment, which is especially useful for an animal constantly exposed to seawater both externally and internally. Mammals, on the other hand, have compartmentalized immune responses depending on how pathogens enter the body (e.g. skin, gut, lungs, etc.). For sharks, this direct 'crosstalk' between peripheral and mucosal immunity might be an evolutionary adaptation to life in the ocean.
These findings showed that the shark pancreas wasn't just involved in digestion, but also functioned ... More as a secondary lymphoid organ, participating in immune surveillance and response. This challenges long-held assumptions that only the spleen played that role in sharks, and opens the door to rethinking how immune systems are structured in other vertebrates (especially those without mammal-like lymph nodes).
This new discovery, the authors highlight, challenges a long-standing view that the spleen is the only organ in sharks capable of organizing and initiating adaptive immune responses. Other organs like the liver, brain, gills, and even the olfactory system have shown signs of immune activity in past studies. But whether they act as full-fledged SLOs hasn't been confirmed. Now that we know the pancreas does, it opens the door to looking more carefully at other tissues. And these implications go beyond sharks. The same tools used here could help uncover hidden immune structures in birds, reptiles, amphibians, and even humans! If the pancreas can act as an immune command center in a jawed vertebrate that split from our lineage over 400 million years ago, what other secrets are we missing about immune system evolution? The absence of lymph nodes in these ancient species might suggest that evolution found… other ways… to build efficient immune surveillance networks.
The nurse shark has offered us a glimpse into a system that works without the blueprint we've come to expect. Understanding these alternative immune strategies might help us design better therapies or vaccines by revealing overlooked immune pathways in our own bodies. For now, the nurse shark's pancreas reminds us that sometimes, looking at things differently — both literally and scientifically — can shift the entire narrative.