Paneth Cells and Their Association With Crohn's Disease

Updated on March 20, 2018
AliciaC profile image

Linda Crampton is a writer and teacher with a first class honors degree in biology. She often writes about the scientific basis of disease.

Inflammation in Crohn's disease may occur anywhere in the digestive tract but often develops in the ileum.
Inflammation in Crohn's disease may occur anywhere in the digestive tract but often develops in the ileum. | Source

Paneth cells are found in the glands located in the lining of the small intestine. The cells perform vital functions, including the secretion of antimicrobial chemicals that fight harmful organisms in the intestine. Paneth cells contribute to innate immunity, a system by which the body blocks or fights invaders immediately or soon after they enter the body. The cells play a major role in keeping the intestinal lining in good condition. Researchers have discovered that misfunctioning Paneth cells are linked to Crohn's disease.

Crohn's disease is a type of inflammatory bowel disease, or IBD. People with the disease have patches of inflamed intestinal lining. The disorder is a painful and sometimes debilitating condition. Its cause isn't completely understood. It's thought to arise due to a combination of a genetic predisposition, an environmental factor, and misbehavior of the immune system.

Paneth cells are named after Joseph Paneth, a nineteenth-century Austrian physiologist. He studied the structure of the cells, although he didn't discover them. Since the cells are named after a person, the word "Paneth" is capitalized. Crohn's disease is named after a gastroenterologist named Burrill Bernard Crohn. In 1932, Crohn and two of his colleagues described the typical pattern of intestinal inflammation found in the disease.

Paneth cells are located in the intestinal glands or crypts located between the villi.
Paneth cells are located in the intestinal glands or crypts located between the villi. | Source

In the simplified illustration of villi and an intestinal gland (or crypt) shown above, all of the cells look the same. In reality, different types of cells are present, though the enterocytes are the most abundant kind on the surface of the villi. Mature enterocytes contribute to digestion and absorb nutrients. The "lumen" of the small intestine is the passageway through which food passes.

Villi and Intestinal Glands or Crypts

The lining of the intesting is covered with folds, or villi. These increase the area for absorption of food. The intestinal glands are located between the villi. They are also known as intestinal crypts and as crypts of Lieberkühn. The word "gland" is used in their name because they produce secretions. They are sometimes referred to as crypts because they are located below the level of the villi. Paneth cells are located at the bottom of the crypts.

The outer cell layer of the villi is known as epithelium. The epithelium extends into the crypts, as shown in the illustration above. Stem cells are located near the paneth cells at the bottom of the crypt. These make new epithelial cells. Replacement of the cells is necessary because the epithelium on the surface of the villi is regularly shed. New cells migrate upwards to replace the old ones on the surface of the villi. An epithelial cell generally lives for three to five days before it's shed.

The stem cells also make new Paneth cells. These stay at the bottom of the crypt instead of migrating upwards, however. Unlike other epithelial cells, Paneth cells may live from three weeks to a month or more.

A section of the small intestine lining that has been stained and magnified
A section of the small intestine lining that has been stained and magnified | Source

The Intestinal Microbiome

A large community of bacteria and other microbes inhabits our intestine. Many of the microbes are known or thought to help us. The effects of others are unknown. Some are harmful. The harmful forms are often kept in check by the "good" microbes, but this isn't always the case.

Bacteria are the most common kind of microbe in the digestive tract. They can be found in the lumen of the intestine, on the surface of the intestinal lining or mucosa, and attached to the surface of the epithelial cells. Under normal circumstances, they don't enter or travel through the mucosa, however. The activities of the Paneth cells help to stop the bacteria from penetrating the mucosa.

Intestinal Gland and Paneth Cell Location

Most Paneth cells are located in the small intestine. They appear to be present in every intestinal gland. They may also be scattered through the large intestine, however.

Paneth Cells

A Paneth cell has a nucleus at its base and numerous large granules in its cytoplasm. The granules contain antimicrobial substances, immune modulators, and trophic factors. These chemicals are released into the lumen of the intestinal gland in order to maintain the health of the intestine. An immune modulator is a substance that helps the body by stimulating or inhibiting the immune system. Trophic factors are chemicals that support the survival of cells. Paneth cells also secrete chemicals that support the neighbouring stem cells.

Antibacterial Functions of Paneth Cells

Paneth cells are small in number but important for the health of the intestinal lining. One type of antimicrobial chemical produced by the cells is a kind known as alpha-defensins, or cryptdins. The chemicals are peptides, or short chains of amino acids. They have positively charged regions that bind to negatively charged regions of phospholipid molecules in cell membranes. As a result, a pore is created in the membrane that kills the cell. Bacteria have more negative regions in their cell membranes than we do, so the defensins bind to them more often than to our cells, killing the bacteria.

Paneth cells also secrete at least two other antimicrobial substances: lysozyme and phospholipase A2. Lysozyme is also found in saliva. It causes bacteria cells to break open, killing the microbe. The process is known as lysis.

Antigens of intestinal bacteria (molecules on their surface) stimulate Paneth cells to release antibacterial chemicals from their vesicles into the lumen of the intestinal gland. The chemicals then attack the bacteria. This behaviour is similar to that of certain white blood cells in the immune system.

The arrow is pointing to a Paneth cell
The arrow is pointing to a Paneth cell | Source

Autophagy

Autophagy is the process in which a cell destroys damaged structures that it contains. New structures replace the old ones. Infective microbes that enter the cell may also be destroyed by autophagy.

The process is especially important in cells that live for a long time, such as Paneth cells. If autophagy doesn't occur in the cells, damage may accumulate over time and the risk of infection by microbes increases. Autophagy when necessary is essential in order for Paneth cells to stay healthy and continue releasing protective chemicals for the intestine.

In animals, researchers have discovered that if Paneth cell autophagy is disrupted by mutated genes, specific drugs, or the presence of certain viruses, the risk of intestinal inflammation is increased.

Crohn's Disease

Inflammatory bowel disease is an inflammatory condition of the lining of the small and /or large intestine. "Bowel" is another word for intestine. The main kinds of IBD are Crohn's disease and ulcerative colitis.

In Crohn's disease (CD), inflammation may be present anywhere in the digestive tract. The areas that are most often affected are the ileum (the last part of the small intestine) and the colon. The inflammation may extend deep into the intestinal lining. Common symptoms include abdominal pain, diarrhea, fatigue, and weight loss.

Anyone with abdominal problems or with symptoms that might indicate the presence of Crohn's disease should visit a doctor for a diagnosis and treatment.

An Interesting Experiment in Mice

A group of US researchers recently explored Paneth cell dysfunction in mice. Mice are often used as a model for the human body. The researchers discovered that autophagy in Paneth cells is necessary in order to destroy at least one kind of parasite.

The researchers "turned off" autophagy in the Paneth cells of the mice by preventing the production of a required protein. They then infected the rodents with an intestinal parasite called Toxoplasma gondii. With the Paneth cells out of action, the parasite was able to enter the intestinal lining, resulting in inflammation and destruction of intestinal glands.

Paneth cells are like the guardians of the intestine and autophagy is like their armor.

— Felix O. Yarovinsky, M.D. via ScienceDaily
Experiments in mice often—but not always—apply to humans.
Experiments in mice often—but not always—apply to humans. | Source

The Link Between Paneth Cells and CD

Research in lab animals has shown that the misfunctioning of Paneth cells is linked to intestinal inflammation. Researchers have found evidence that this is also the case in humans. The relationship between Paneth cells and CD in humans isn't completely clear, however. Researchers can't deliberately disable Paneth cells in humans as they've done in mice, so it's harder to reach definite conclusions.

It's important to note that scientists describe the relationship between Paneth cells and Crohn's disease in humans as an association or a link. Some discoveries could indicate that inflammation in the intestine happens first and then the inflammation damages the Paneth cells. Nevertheless, the cells do seem to play a role in CD.

Researchers believe that there are multiple types of Crohn's disease. Paneth cell dysfunction may be more important in some types than others.

Paneth cells mediate immunity and maintain the small intestinal epithelium; defects in activities of these cells have been observed in high proportions of patients with CD, and are associated with a more aggressive CD phenotype.

— Stappenbeck and McGovern, Gastroenerology Journal
Item 5 is the rough endoplasmic reticulum, which processes proteins. The ribosomes on the surface make proteins.
Item 5 is the rough endoplasmic reticulum, which processes proteins. The ribosomes on the surface make proteins. | Source

ER Stress and the Unfolded Protein Response

Disruption of autophagy in Paneth cells may lead to serious damage in the cells and intestinal inflammation. Problems in Paneth cells may be related to Crohn’s disease via a condition known as ER stress instead of or as well as autophagy, however.

The endoplasmic reticulum or ER is a network of membranous tubes in a cell. The ER has very important functions in the life of a cell. It's involved in both the synthesis and the transport of proteins.

Proteins have a complex shape and a highly folded structure. The folds aren't random. The correct shape of a protein is vital in order for it to function properly. Unfolded or misfolded proteins can be useless or even dangerous for a cell.

As in the intestine, the space inside the endoplasmic reticulum tubes is known as the lumen. When unfolded proteins are present in the lumen, ER stress is said to exist and the unfolded protein response or UPR is activated. During this response, protein synthesis is reduced in the body, damaged proteins in the ER are broken down, and processes that cause protein folding are stimulated. If this doesn't improve the situation, apoptosis occurs. Apoptosis is self destruction of the cell.

ER Stress in Other Epithelial Cells

Other cells in the endothelium besides Paneth cells include goblet cells, enteroendocrine cells, and enterocytes. All of these cells make and secrete proteins or peptides and may be affected by the UPR. Proteins consist of long chains of amino acids. A peptide is made of a short chain.

Goblet cells secrete mucin, which is a major component of mucus. The mucus coats and protects the lining of the intestine. The enteroendocrine cells secrete hormones. The enterocytes secrete chemical signaling molecules and produce digestive enzymes. All of these substances are proteins or peptides.

The UPR and Crohn's Disease

The endoplasmic reticulum and protein folding are very important in Paneth cells and in the lives of the other secretory cells in the intestinal epithelium. Researchers say that ER stress that hasn't been removed or an unfolded protein response that isn't working properly can cause the death of Paneth cells, damage to the intestinal lining, and inflammation in the area. The inflammatory response develops when tissues are injured in the body. It's often helpful, but inflammation that continues for a long time or is severe can be harmful.

Scientists think that genetic and/or environmental factors are ultimately responsible for CD, but they say that evidence suggests that unresolved ER stress in Paneth cells and perhaps in other endothelial cells mediates the action of a genetic or environmental factor.

The Importance of Further Research

Understanding the functions and activities of Paneth cells may be of more than academic interest. If researchers learn enough about the causes of autophagy and misfolded proteins and about the link between Paneth cells and Crohn's disease, they may be able to create new treatments for at least some forms of the disease. One promising area of research related to misfolded proteins is the use of molecular chaperones as medicines. These are proteins which help other proteins to fold correctly.

The research related to CD may have benefits in additional ways. Misfolded proteins in the brain play a major role in some very unpleasant disorders, including Alzheimer's disease and Parkinson's disease. As the video above states, they are also involved in diabetes and cancer. It may be a big leap from misfolded proteins in the Paneth cells of the intestine to misfolded ones in other parts of the body. On the other hand, studying problematic proteins and the unfolded protein response may be very helpful for dealing with a variety of health disorders, wherever they occur.

References

  • Information about Paneth cells from Colorado State University
  • Paneth cell functions (abstract) from the NIH or National Institutes of Health
  • Facts about Paneth cells from Cell (an Elsevier journal) http://www.cell.com/current-biology/pdf/S0960-9822(14)00487-4.pdf
  • Alterations in Paneth cells linked to Crohn's disease from the Gastroenterology Journal (abstract)
  • University of Rochester Medical Center. (2018, February 8). Gut bacteria can be good, and bad, for health: Rare group of cells could inform development of therapies for inflammatory bowel disease. ScienceDaily. Retrieved February 10, 2018 from www.sciencedaily.com/releases/2018/02/180208131707.htm [Note: The passageway through which food passes is called the digestive tract, not the digestive track. The latter term is used in the news release.]
  • Loss of Paneth cell autophagy in mice (free highlights and summary) from the Cell Host and Microbe journal
  • Endoplasmic reticulum stress and unfolded protein response in inflammatory bowel disease (abstract) from the NIH
  • Intestinal epithelial cell ER stress and IBD from the Frontiers in Immunology journal

Questions & Answers

  • What is Paneth cell metaplasia?

    Paneth cell metaplasia is the appearance of Paneth cells where they aren't normally found. The cells are most abundant in the small intestine. In a healthy person, they are also scattered at the start of the large intestine, and aren't seen in the rest of the organ. In some people with Crohn's disease or ulcerative colitis, however, Paneth cells have been discovered further along in the large intestine. The reason for this observation isn't fully understood.

© 2018 Linda Crampton

Comments

    0 of 8192 characters used
    Post Comment

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      4 months ago from British Columbia, Canada

      Hi, Glenn. Thank you for the visit and the comment. I'm sorry that your niece has Crohn's disease. It can be a horrible illness.

    • Glenn Stok profile image

      Glenn Stok 

      4 months ago from Long Island, NY

      Linda, Your article was very informative. My niece has Crohn’s Disease and I know how she suffered with it.

      It’s interesting how the Paneth cells are responsible for killing the bacteria in the intestines and when it malfunctions the intestines can become irritated.

      Thanks to your detailed article, I now have a better understanding of what is actually going on.

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      8 months ago from British Columbia, Canada

      Thank you very much, Audrey. I appreciate your kind comment.

    • vocalcoach profile image

      Audrey Hunt 

      8 months ago from Idyllwild Ca.

      We're learning more each day about diseases. This article is a marvelous explanation about Paneth Cells. I've learned so much about health and disease from your hubs and I'm very grateful to you, Linda.

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      8 months ago from British Columbia, Canada

      Thank you very much for the comment, Nithya.

    • Vellur profile image

      Nithya Venkat 

      8 months ago from Dubai

      A very well researched article explaining about the Paneth cells. Folding and unfolding of proteins play such an important role, this I now know after reading your article. Thank you for sharing.

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      8 months ago from British Columbia, Canada

      Thank you, Devika. I appreciate your visit.

    • DDE profile image

      Devika Primić 

      8 months ago from Dubrovnik, Croatia

      Hi Linda you know how to share your knowledge on so many different health issues. Important and information for everyone.

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      8 months ago from British Columbia, Canada

      The experiences that you describe sound horrible, Natalie. I hope so much that new and more effective treatments appear soon. Thank you for the comment.

    • Natalie Frank profile image

      Natalie Frank 

      8 months ago from Chicago, IL

      Linda - I've know several people with this disease and they all had horrific surgeries and colostomies, one of whom couldn't have it reversed. This is such an eye opening article. Thank you for writing it.

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      8 months ago from British Columbia, Canada

      Hi, Peggy. Yes, it must be horrible to live with the disease. I hope the research into unfolded proteins increases. It's certainly interesting that they've been implicated in a variety of illnesses.

    • Peggy W profile image

      Peggy Woods 

      8 months ago from Houston, Texas

      The more researchers discover the greater chance that cures may someday follow. It must be terrible to have to live with Crohn's Disease. It is interesting to discover that those unfolded proteins might also be responsible for other diseases as well.

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      8 months ago from British Columbia, Canada

      Hi, Heidi. Thank you for sharing the information about your Dad. I hope even better treatments for Crohn's disease are discovered soon.

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      8 months ago from British Columbia, Canada

      Hi, Dora. I appreciate your comment very much.

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      8 months ago from British Columbia, Canada

      The situation must have been very hard for your student, Bill. It's hard for adults, too, but it must be especially difficult for a school student.

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      8 months ago from British Columbia, Canada

      Hi, Mary. Understanding how the body works is useful. I think it's very interesting, too!

    • heidithorne profile image

      Heidi Thorne 

      8 months ago from Chicago Area

      My dad had this and it was life altering. Back in his day, it required major surgery for him. Luckily, today there are medications to address the inflammation and other effects. Thanks for sharing this in-depth discussion!

    • MsDora profile image

      Dora Weithers 

      8 months ago from The Caribbean

      Despite the vocabulary challenges for me, I understand the importance of Paneth cells and autophagy to the digestive and overall health. You are an excellent teacher. Thanks for sharing these important lessons.

    • billybuc profile image

      Bill Holland 

      8 months ago from Olympia, WA

      I had a student once with Crohn's Disease...painful and very embarrassing for a twelve year old....thank you for clarifying some things for me.

    • aesta1 profile image

      Mary Norton 

      8 months ago from Ontario, Canada

      Linda, I feel like being back to school but learning this time about things I should have learned before. It is so important to understand how our body functions so we can make ourselves more healthy.

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      8 months ago from British Columbia, Canada

      Thank you very much for the comment and for sharing the information, Manatita. I appreciate your visit, as always.

    • manatita44 profile image

      manatita44 

      8 months ago from london

      A very interesting Hub. I see the iimportance that Paneth cells have to play in fighting or reducing inflammation and I note the crucial importance of the bowels in this respect.

      Actually I take probiotics or Psyllium husks or both. Dr Grundy also has a prebiotic designed to aid the good bacteria to fight against the bad. I have taken this in the past.

      An interesting one, Crohns and explained very well in terms of pathology.

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      8 months ago from British Columbia, Canada

      Hi, Jackie. No, you didn't miss anything. Diagnosing Crohn's disease wasn't part of my topic. From what I've read, a variety of tests are used to confirm the presence of the disease. A tissue biopsy may be one of them.

    • AliciaC profile imageAUTHOR

      Linda Crampton 

      8 months ago from British Columbia, Canada

      Thank you very much, Flourish. I appreciate your kind comment a great deal. I suspect that you're right about the connection between diseases and the role of the digestive system. Some fundamental processes in the body may be a common factor in many diseases.

    • Jackie Lynnley profile image

      Jackie Lynnley 

      8 months ago from The Beautiful South

      Would biopsy of the upper and lower stomach show these diseases? Did I overlook how you would be tested for these? Very interesting and I would like to know. Perhaps in the videos I have not yet watched?

    • FlourishAnyway profile image

      FlourishAnyway 

      8 months ago from USA

      I marvel at your ability to explain complicated disease processes like this. I think ultimately we will find that many diseases are connected in ways we didn’t expect, many of them to our digestive system and the world within it. The old adage about you are what you eat certainly deserves merit, not to knock genetic predisposition. Well done!

    working

    This website uses cookies

    As a user in the EEA, your approval is needed on a few things. To provide a better website experience, owlcation.com uses cookies (and other similar technologies) and may collect, process, and share personal data. Please choose which areas of our service you consent to our doing so.

    For more information on managing or withdrawing consents and how we handle data, visit our Privacy Policy at: https://owlcation.com/privacy-policy#gdpr

    Show Details
    Necessary
    HubPages Device IDThis is used to identify particular browsers or devices when the access the service, and is used for security reasons.
    LoginThis is necessary to sign in to the HubPages Service.
    Google RecaptchaThis is used to prevent bots and spam. (Privacy Policy)
    AkismetThis is used to detect comment spam. (Privacy Policy)
    HubPages Google AnalyticsThis is used to provide data on traffic to our website, all personally identifyable data is anonymized. (Privacy Policy)
    HubPages Traffic PixelThis is used to collect data on traffic to articles and other pages on our site. Unless you are signed in to a HubPages account, all personally identifiable information is anonymized.
    Amazon Web ServicesThis is a cloud services platform that we used to host our service. (Privacy Policy)
    CloudflareThis is a cloud CDN service that we use to efficiently deliver files required for our service to operate such as javascript, cascading style sheets, images, and videos. (Privacy Policy)
    Google Hosted LibrariesJavascript software libraries such as jQuery are loaded at endpoints on the googleapis.com or gstatic.com domains, for performance and efficiency reasons. (Privacy Policy)
    Features
    Google Custom SearchThis is feature allows you to search the site. (Privacy Policy)
    Google MapsSome articles have Google Maps embedded in them. (Privacy Policy)
    Google ChartsThis is used to display charts and graphs on articles and the author center. (Privacy Policy)
    Google AdSense Host APIThis service allows you to sign up for or associate a Google AdSense account with HubPages, so that you can earn money from ads on your articles. No data is shared unless you engage with this feature. (Privacy Policy)
    Google YouTubeSome articles have YouTube videos embedded in them. (Privacy Policy)
    VimeoSome articles have Vimeo videos embedded in them. (Privacy Policy)
    PaypalThis is used for a registered author who enrolls in the HubPages Earnings program and requests to be paid via PayPal. No data is shared with Paypal unless you engage with this feature. (Privacy Policy)
    Facebook LoginYou can use this to streamline signing up for, or signing in to your Hubpages account. No data is shared with Facebook unless you engage with this feature. (Privacy Policy)
    MavenThis supports the Maven widget and search functionality. (Privacy Policy)
    Marketing
    Google AdSenseThis is an ad network. (Privacy Policy)
    Google DoubleClickGoogle provides ad serving technology and runs an ad network. (Privacy Policy)
    Index ExchangeThis is an ad network. (Privacy Policy)
    SovrnThis is an ad network. (Privacy Policy)
    Facebook AdsThis is an ad network. (Privacy Policy)
    Amazon Unified Ad MarketplaceThis is an ad network. (Privacy Policy)
    AppNexusThis is an ad network. (Privacy Policy)
    OpenxThis is an ad network. (Privacy Policy)
    Rubicon ProjectThis is an ad network. (Privacy Policy)
    TripleLiftThis is an ad network. (Privacy Policy)
    Say MediaWe partner with Say Media to deliver ad campaigns on our sites. (Privacy Policy)
    Remarketing PixelsWe may use remarketing pixels from advertising networks such as Google AdWords, Bing Ads, and Facebook in order to advertise the HubPages Service to people that have visited our sites.
    Conversion Tracking PixelsWe may use conversion tracking pixels from advertising networks such as Google AdWords, Bing Ads, and Facebook in order to identify when an advertisement has successfully resulted in the desired action, such as signing up for the HubPages Service or publishing an article on the HubPages Service.
    Statistics
    Author Google AnalyticsThis is used to provide traffic data and reports to the authors of articles on the HubPages Service. (Privacy Policy)
    ComscoreComScore is a media measurement and analytics company providing marketing data and analytics to enterprises, media and advertising agencies, and publishers. Non-consent will result in ComScore only processing obfuscated personal data. (Privacy Policy)
    Amazon Tracking PixelSome articles display amazon products as part of the Amazon Affiliate program, this pixel provides traffic statistics for those products (Privacy Policy)