Prostanoid receptor 2 signaling protects T helper 2 cells from BALB/c mice against activation-induced cell death.
T helper 2 (Th2) cells play a central role in the progression of many diseases such as allergic airway inflammation, autoimmune diseases, and infections caused by intracellular pathogens. Consequently, animals such as BALB/c mice, which exhibit a propensity for generating Th2 responses, are susceptible to allergic airway inflammation, type-II autoimmune diseases, and various infections induced by intracellular pathogens, namely, Leishmania. In contrast, C3H/OuJ mice have a tendency for generating T helper 1 (Th1) responses and show resistance to these diseases. Here, we show that prostaglandin endoperoxide E(2) selectively inhibits activation-induced cell death of Th2 cells by signaling through its receptor E-prostanoid receptor 2 (EP2). Consequently, Th2 cells derived from BALB/c mice expressed very high levels of EP2. On the other hand, Th2 cells derived from C3H/OuJ mice expressed very low levels of EP2, which failed to support the survival of Th2 cells. Furthermore, we found that this effect of EP2 on Th2 cells from BALB/c mice was executed by a granzyme B-mediated mechanism. EP2 belongs to a group of G-protein-coupled receptors that are amenable to therapeutic targeting. Our findings therefore identify EP2 as a promising target for small molecule-directed immunomodulation.
Immunology Group, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Vandana
V
Kaul
Luc
L
Van Kaer
Gobardhan
G
Das
Jyoti
J
Das
D000818:Animals; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011449:Prostaglandin Endoperoxides / Q000235:genetics / Q000276:immunology; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D011449:Prostaglandin Endoperoxides; D058307:Receptors, Prostaglandin E, EP2 Subtype; D015232:Dinoprostone