Anti-T-cell Ig and mucin domain-containing protein 1 antibody decreases TH2 airway inflammation in a mouse model of asthma.

Background: The T-cell Ig and mucin domain-containing (TIM) gene locus has been linked to differences in T(H)2 responsiveness and asthma susceptibility in mice. The homologous locus in human subjects harbors the gene for TIM-1, which encodes a receptor for hepatitis A virus and has been linked with decreased susceptibility to atopic disease in hepatitis A virus-seropositive individuals.

Objective: We investigated the effects of administering antibodies against TIM-1 in a mouse model of allergic asthma to determine whether the treatment could downregulate T(H)2 cytokines and reduce pulmonary inflammation.

Identification and characterization of a cell-surface receptor, P2Y15, for AMP and adenosine.

AMP and adenosine are found in all cell types and can be released by cells or created extracellularly from the breakdown of ATP and ADP. We have identified an orphan G protein-coupled receptor with homology to the P2Y family of nucleotide receptors that can respond to both AMP and adenosine. Based on its ability to functionally bind the nucleotide AMP, we have named it P2Y15.

Chemoattractant receptor-homologous molecule expressed on Th2 cells activation in vivo increases blood leukocyte counts and its blockade abrogates 13,14-dihydro-15-keto-prostaglandin D2-induced eosinophilia in rats.

We cloned, expressed, and characterized in vitro and in vivo the gene encoding the rat ortholog of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), a G protein-coupled receptor for prostaglandin D2 (PGD2). Quantitative reverse transcription-polymerase chain reaction analysis demonstrated highest CRTH2 expression in the lung, brain, ovary, and spleen. Pharmacologically, rat CRTH2 stably transfected in mouse preB lymphoma L1.