Instead of protecting the body, the immune system can sometimes become unbalanced, as caused by a cellular immune response in autoimmune diseases andObserve allergiesis. A team from the Ludwig Maximilian University in Munich studied how mast cells regulate their calcium levels to keep this response under control.
What is a cellular immune response?
The immune system protects every living being from attacks by viruses and bacteria and also helps to eliminate cancer cells. Innate immunity is responsible for the initial detection and destruction of invasive pathogens. It then alerts the cells of the adaptive immune system, which eliminates infectious organisms and provides long-term protection against them. However, there are situations in which the cellular immune response can be misdirected. In this case, the immune system focuses its firepower on the wrong targets. This can happen either due to the body's own proteins in autoimmune diseases or to harmless foreign proteins in the case of allergies. Recently, a research team led by immunopharmacologist Susanna Zierler and pharmacologist Ingrid Boekhoff from the Walther Straub Institute for Pharmacology and Toxicology has now shown that the activity of certain ion channel proteins in mast cells plays an important role in preventing allergic and anaphylactic reactions. This ensures that the cellular immune response does not overdrive.
Mast cells are found in virtually all organs of the body. They regulate the initiation and resolution of inflammatory reactions of the immune system to combat infections and metabolic disorders. Immune responses are highly complex processes that must be carried out carefully. This means that immune cells must be able to recognize specific signals that interact with receptor proteins on the cell surface. These reactions include changes in levels of positively charged ions, including calcium, sodium and potassium. It turns out that rapid and transient changes in ion concentrations are essential for the activation of many types of immune cells. It is clear that cells regulate intracellular levels of these ions primarily through proteins. Researchers refer to these as ion channels and ion pumps.
Research results
The research groups have now characterized the functions of ion channels that selectively regulate the concentration of free calcium in mast cells. They also examined how many other cell types of mast cells achieve this by activating the release of calcium from intracellular stores. The endoplasmic reticulum (ER) is the largest calcium storage organelle in cells. But other intracellular organelles such as the mitochondria (power plants of the cell) and the lysosomes (intracellular waste disposal units) can also supply calcium ions when required. All of these intracellular compartments are bounded by membranes into which specialized ion channels are inserted. Zierler, Boekhoff and their colleagues report that one of these, TPC1, plays an important role in regulating changes in the intracellular distribution of calcium ions between endolysosomes and the ER.
The researchers showed that selective genetic knockout or pharmacological inhibition of TPC1 in mast cells in mice alters the balance between the amounts of calcium stored in these organelles. Crucially, this change is associated with a significant increase in histamine secretion, which then triggers a severe allergic reaction at both the cellular and systemic levels. These results show that disruption of the delicately regulated balance that controls the content of intracellular calcium ions in mast cells can lead to drastic allergic and anaphylactic reactions. The identification of the TPC1 channel protein as an important regulator of mast cell activity and histamine secretion has clear therapeutic implications.This studyshows the TPC1 channel as a promising active ingredient for the treatment of allergic and similar diseases. Overall, targeted pharmacological control of ion channels in immune cells offers great potential. This is a great prospect for the treatment of infections, allergies and possibly even leukemia.
