Prostanoid receptor 2 signaling protects T helper 2 cells from BALB/c mice against activation-induced cell death.

Kaul V, Van Kaer L, Das G, Das J
J Biol Chem. 2012 287 (30): 25434-9

PMID: 22654101 · PMCID: PMC3408175 · DOI:10.1074/jbc.C111.324707

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.

MeSH Terms (12)

Animals Cell Death Cell Survival Dinoprostone Female Lymphocyte Activation Mice Mice, Inbred BALB C Prostaglandin Endoperoxides Receptors, Prostaglandin E, EP2 Subtype Signal Transduction Th2 Cells

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