The Unsung Heroes of Intestinal Health
Written By Renee Lee
Edited By Gesi Huang
Inflammatory bowel diseases (IBDs), such as Crohn’s or ulcerative colitis, while not uncommon, remain quite mysterious in terms of cause. An important actor that may have been overlooked in these diagnoses, however, is the highly secretory Paneth cell found in the small intestine of many omnivores. These cells are characterized by elevated levels of antimicrobial peptide (AMP) production, which assist in the process of host defense against bacteria. Research on these cells is currently limited, but the complex roles of its secretions hint at a crucial purpose in the digestive system.
Paneth cells reside in Lieberkühn crypts, located at the bottom of intestinal linings where stem cells are found. Healthy Paneth cells help replenish cells at the bottoms of these crypts by expressing important growth factors, including Wnt3 and epidermal growth factor (EGF). Research has revealed that when Paneth cells become impaired, the maintenance of epithelial and stem cells becomes compromised, suggesting that Paneth cell dysfunction may be a major contributing factor to the health of the intestinal epithelium. Additionally, Paneth cell-secreted AMPs are found localized in the mucus to prevent bacterial invasions, highlighting the antimicrobial properties of Paneth cells.
Photos by Edward Jenner (left) and Sora Shimazaki (right). Curated by Leticia De Almeida Smolka (lds234@cornell.edu).
Many of the challenges in studying Paneth cells arise from the lack of proper technique required to track its development. A major question that remains unanswered is how Paneth cells can sense and locate bacteria, though a popular theory is that the ability depends on a gene known as nucleotide-binding and oligomerization domain 2 (NOD2). The expression of α‐defensins, which are a type of AMP usually secreted in response to bacteria, appears to be dependent on the NOD2 gene, as experiments on NOD2 knockout mice have reportedly shown a diminished expression of several α‐defensins (Garcia-Gonzalez, Libert, & Wallaeys, 2022).
To revisit the overarching role of Paneth cells in intestinal immune defense, it is important to note that in forms of Crohn’s disease associated with NOD2 gene mutations, Paneth cells tend to show structural abnormalities or reduced secretions, notability that of defensins. In other similar inflammatory bowel diseases, Paneth cells exhibit signs of stress and unusual amounts of cell death. While researchers are unable to conclude whether Paneth malfunction is a cause or consequence of IBDs, evidence exists to suggest that deterioration of Paneth cell health or function can contribute to such pathology.
The exact mechanistic details of the role of Paneth cells in the body remain shrouded in mystery. Nonetheless, they spotlight the importance of carrying out niche research in relatively new fields. Research is an ever-evolving field, and in an age of rapidly developing technology, it becomes all the more important to explore the unknowns. Furthermore, answering biomedical questions not only sheds light on many mysteries of the human body, but also drives forward the development of potent treatments and medications.
Renee Lee ’27 is in the College of Arts and Sciences. She can be reached at ryl27@cornell.edu.
