Tissue-resident T cells are killed by tissue damage after injury

Regina Stark, scientist at the department of Hematopoiesis of Sanquin, uncovered that tissue-resident T cells are killed by tissue damage after injury. Her research will help to better understand how immune responses in tissues are regulated and may lead to the discovery of new therapies for autoimmune diseases. The work is published in Science Immunology.

Immune cells do not only circulate through the blood, but are also found in tissues like the intestine, liver and lung. Within these tissues, specialized tissue-resident T cells are important for protection against local reinfections. These T cells are in alert mode to react fast when an infection hits. To minimize the collateral damage or autoimmunity that these T cells can cause, they need to be tightly regulated to maintain tissue homeostasis.

Suicide program

Regina Stark studied how T cells react when tissue is injured and damaged. Molecules released upon tissue damage are notorious for triggering unwanted immune responses that aggravate the damage. She uncovered how T cells prevent further damage by activating a suicide program that leads to their removal.

That suicide program is induced by the receptor P2RX7, which detects molecules that are released during tissue damage. This pathway will only be activated in the absence of other specific activation signal, such as T cell receptor triggering. In contrast to the tissue resident T cells, bypassing circulating T cells lack this pathway.

New therapies for autoimmune diseases

This new level of regulation could be a safeguard mechanism to prevent that the highly alerted tissue resident T cells lead to excessive immunopathology. These novel findings might help to discover new therapies for autoimmune diseases.


RM maintenance is regulated by tissue damage via P2RX7 Stark R, Wesselink T, Behr FM, Kragten NAM, Arens R, Koch-Nolte F, van Gisbergen KPJM, van Lier RAW.  2018 Dec 14;3(30). 

This work is financed by the Netherlands Organisation for Scientific Research (NWO).