Mast cell activation by CRF1 contributes to stress-induced disease

Mast cells are innate immune cells situated throughout the human body at the host-environment interface (lungs, gastrointestinal tract, skin, etc). Their location at these sites allows them to quickly respond to pathogens and regulate the immune response through the release of a variety of pre-formed and de novo synthesized mediators. Although mast cells act as critical effector cells of the immune response, in some instances, their activation can have unintended, deleterious consequences. One of the most widely understood examples of this is the release of histamine by mast cells. As a mediator, histamine facilitates the movement of important immune cells and other mediators to the site of infection or injury but can also cause many of the hallmark symptoms of an allergic reaction.

Mast cells are a versatile cell type and can also be activated by neurotransmitters during the stress response. The stress response is a normal physiological response intended to protect an individual. However, during times of prolonged stress or chronic stress, this response can have many negative effects and is associated with the onset of diseases such as Irritable Bowel Syndrome, Inflammatory Bowel Disease, and Gastroesophageal Reflux Disease, to name a few. During the stress response, the hormone corticotropin-releasing factor (CRF) is released centrally and peripherally leading to a series of downstream responses. Mast cells express both CRF receptor subtypes, CRF1 and CRF2, but little is known about this signaling pathway in mast cells. Recent research led by Dr. Adam Moeser at Michigan State University is shedding light on the mast cell’s role in mediating the negative effects of stress through CRF activation. Their findings were recently published in the Journal of Leukocyte Biology.

To definitively look at the role of mast cell-specific CRF1 signaling in the stress response, the Moeser lab utilized transgenic mice that lack mast cells throughout their body. These transgenic mice can have mast cell populations restored by injecting mast cells grown in culture. Two groups of mast cell-deficient mice were used, where one group was injected with wild-type mast cells that express both CRF1 and CRF2 while the other group was injected with mast cells lacking CRF1. After several months, the mice were subjected to psychological stress or exposed to allergens to cause an allergic reaction. The mice with mast cells lacking CRF1 had significantly lower levels of histamine in response to psychological stress and in response to the allergen when compared to mice with both CRF1- and CRF2-expressing mast cells. The lower levels of histamine were accompanied by improved clinical symptoms in response to stress and allergen.

These findings by the Moeser lab indicate that signaling through mast cell CRF1 highly activates mast cells to release histamine that leads to a negative impact on health. Stress has been associated with the onset of a variety of diseases, but the mechanisms are not well understood. By understanding the importance of the mast cell CRF receptor signaling pathways in regulating mast cell activation and subsequent clinical symptoms, more effective therapeutics can be developed to treat stress-related diseases.

If you research mast cells or the stress response, check out the Human Mast Cell Line (LUVA) from the University of Virginia, or our other unique reagents for studying innate immunology.