Paneth cells are cells in the small intestine

epithelium Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...

, alongside

goblet cells Goblet cells are simple columnar epithelial cells that secrete gel-forming mucins, like mucin 5AC. The goblet cells mainly use the merocrine method of secretion, secreting vesicles into a duct, but may use apocrine methods, budding off their secre ...

enterocytes Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase it ...

, and

enteroendocrine cells Enteroendocrine cells are specialized cells of the gastrointestinal tract and pancreas with endocrine function. They produce gastrointestinal hormones or peptides in response to various stimuli and release them into the bloodstream for systemic ef ...

. Some can also be found in the

cecum The cecum or caecum is a pouch within the peritoneum that is considered to be the beginning of the large intestine. It is typically located on the right side of the body (the same side of the body as the appendix (anatomy), appendix, to which i ...

and appendix. They are below the intestinal stem cells in the

intestinal glands In histology, an intestinal gland (also crypt of Lieberkühn and intestinal crypt) is a gland found in between villi in the intestinal epithelium lining of the small intestine and large intestine (or colon). The glands and intestinal villi are ...

(also called crypts of Lieberkühn) and the large

eosinophilic Eosinophilic (Greek suffix -phil-, meaning ''loves eosin'') is the staining of tissues, cells, or organelles after they have been washed with eosin, a dye. Eosin is an acidic dye for staining cell cytoplasm, collagen, and muscle fibers. ''Eosi ...

refractile granules that occupy most of their

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...

. These granules consist of several anti-microbial compounds and other compounds that are known to be important in immunity and host-defense. When exposed to

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

or bacterial

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s, Paneth cells secrete some of these compounds into the lumen of the intestinal gland, thereby contributing to maintenance of the gastrointestinal barrier. Paneth cells are named after 19th-century pathologist

Joseph Paneth Joseph Paneth (6 October 1857 – 4 January 1890) was an Austrian physiologist born in Vienna. Paneth is remembered for his description of "Paneth cells", which are cells that provide host defense against microbes in the mucosa of the small int ...

Structure

Paneth cells are found throughout the

small intestine The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the p ...

and the appendix at the base of the

. The Paneth cell increase in numbers towards the end of the small intestine. Like the other epithelial cell lineages in the small intestine, Paneth cells originate at the stem cell region near the bottom of the gland. However, unlike the other epithelial cell types, Paneth cells migrate downward from the stem cell region and settle just adjacent to it. This close relationship to the stem cell region is thought to suggest that Paneth cells are important in defending the gland stem cells from microbial damage, although their function is not entirely known. Furthermore, among the four aforementioned intestinal cell lineages, the Paneth cells live the longest (18–23 days)(just under a month).

Function

Paneth cells secrete antimicrobial peptides and proteins, which are "key mediators of host-microbe interactions, including homeostatic balance with colonizing microbiota and innate immune protection from enteric pathogens." Small intestinal crypts house

stem cells In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...

that serve to constantly replenish

epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

that die and are lost from the villi. Protection of these

is essential for long-term maintenance of the intestinal

, and the location of Paneth cells adjacent to stem cells suggests that they play a critical role in defending epithelial cell renewal.

Sensing microbiota

Paneth cells sense bacteria via MyD88-dependent

toll-like receptor Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are Bitopic protein, single-pass membrane-spanning Receptor (biochemistry), receptors usually expressed on sentinel cells such as macrophage ...

(TLR) activation which then triggers antimicrobial action.

Secretions

The principal defense molecules secreted by Paneth cells are

alpha-defensin Alpha defensins are a family of mammalian defensin peptides of the alpha subfamily. In mammals they are also known as cryptdins and are produced within the small bowel. ''Cryptdin'' is a portmanteau of '' crypt'' and ''defensin''. Defensins are ...

s, which are known as

cryptdin Alpha defensins are a family of mammalian defensin peptides of the alpha subfamily. In mammals they are also known as cryptdins and are produced within the small bowel. ''Cryptdin'' is a portmanteau of '' crypt'' and ''defensin''. Defensins are ...

s in mice. These

peptides Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

have

hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, th ...

and positively charged domains that can interact with

phospholipids Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

in cell membranes. This structure allows defensins to insert into membranes, where they interact with one another to form pores that disrupt membrane function, leading to cell lysis. Due to the higher concentration of negatively charged

phospholipid Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

s in bacterial than vertebrate

cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

s, defensins preferentially bind to and disrupt bacterial cells, sparing the cells they are functioning to protect. Paneth cells are stimulated to secrete defensins when exposed to bacteria (both

Gram positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

and negative types) or such bacterial products as

lipopolysaccharide Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...

muramyl dipeptide Muramyl dipeptide is constituent of both Gram-positive and Gram-negative bacteria composed of N-acetylmuramic acid linked by its lactic acid moiety to the N-terminus of an L-alanine D- isoglutamine dipeptide. It can be recognized by the immune s ...

and

lipid A Lipid A is a lipid component of an endotoxin held responsible for the toxicity of gram-negative bacteria. It is the innermost of the three regions of the lipopolysaccharide (LPS), also called endotoxin molecule, and its hydrophobic nature allows it ...

. In addition to

defensin Defensins are small cysteine-rich cationic proteins across cellular life, including vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, ...

s, Paneth cells secrete

lysozyme Lysozyme (EC 3.2.1.17, muramidase, ''N''-acetylmuramide glycanhydrolase; systematic name peptidoglycan ''N''-acetylmuramoylhydrolase) is an antimicrobial enzyme produced by animals that forms part of the innate immune system. It is a glycoside ...

tumor necrosis factor-alpha Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...

, and

phospholipase A2 The enzyme phospholipase A2 (EC 3.1.1.4, PLA2, systematic name phosphatidylcholine 2-acylhydrolase) catalyse the cleavage of fatty acids in position 2 of phospholipids, hydrolyzing the bond between the second fatty acid “tail” and the glyce ...

. Lysozyme and phospholipase A2 both have clear

antimicrobial An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals ar ...

activity. This battery of secretory molecules gives Paneth cells a potent arsenal against a broad spectrum of agents, including bacteria,

fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...

and even some enveloped

virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...

es. Paneth cells participate in the

Wnt signaling pathway The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling p ...

, which regulates stem cell proliferation in the intestines. Recently, however, it has been discovered that the regenerative potential of intestinal epithelial cells declines over time as a result of aged Paneth cells secreting the protein

Notum The notum (plural nota) is the dorsal portion of an insect's thoracic segment, or the dorsal surface of the body of nudibranch gastropods. The word "notum" is always applied to dorsal structures; in other words structures that are part of the back ...

, which is an extracellular inhibitor of Wnt signaling. If Notum secretion is inhibited, the regenerative potential of the intestinal epithelium could increase.

References

;Bibliography * * {{Authority control Epithelial cells Human cells Gastroenterology

Structure

Function

Sensing microbiota

Secretions

See also

References