Generation of cytokines through the leucocyte immunoglobulin‐like receptors

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SummaryThe LIRs comprise a family of immunoregulatory receptors with activating and inhibitory members as well as soluble forms of the receptors. These receptors are part of the larger context of other families of activating and inhibitory receptors, some of which are closely related members of the immunoglobulin superfamily and others of which are C‐type lectin receptors. In vitro data have demonstrated the capacity of the inhibitory LIRs to regulate the threshold and amplitude of cellular responses to diverse agonists. The emerging data on the activating receptors indicate that they may elicit release of preformed, granule‐associated mediators, de novo lipid mediator generation and cytokine release either from preformed stores or by gene induction. The identification of ligands for the LIRs is limited currently to the recognition of a broad array of MHC class I molecules by LIR1 and LIR2 (and possibly LIR6). Gene disruption studies of the closest mouse homologues of the inhibitory LIRs support the hypothesis that the LIRs may regulate inflammatory responses, particularly those dependent on the mast cell and/or Th2 cell‐dependent humoral responses. The relative balance of inhibitory and activating LIRs expressed by a particular cell, the differential regulation of their putative ligands, whether endogenous host‐related or exogenous pathogen‐related, and the exposure of the LIRs to those ligands may play an important role in determining cellular activation responses and the development and resolution of tissue inflammation.