ABSTRACT
The activation of immune system cells involved in inflammatory diseases such as asthma was for many years thought to be regulated almost exclusively by activating stimuli such as antigen specific antibody, adhesion molecule ligands, and cytokines. Over the last few years, it has become apparent that most cells of the hematopoietic system express cell-surface receptors that inhibit activation responses in vitro through a shared cytoplasmic amino acid sequence, termed the immunoreceptor tyrosine-based inhibitory motif (ITIM). ITIM-bearing receptors belong to two superfamilies that are defined by their extracellular domain sequences, namely, the immunoglobulin (Ig) and C-type lectin superfamilies. The mechanisms by which the inhibitory receptors suppress activation responses, the identification of their ligands, and the effects of receptor deficiency in animal models are currently the subjects of considerable investigation, as is the search for additional ITIM-bearing receptors. The animal studies have revealed that many types of inflammation are counterregulated in vivo by inhibitory receptors. Hence, these receptors represent potential therapeutic targets for suppressing chronic inflammation in diseases such as asthma.
