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J Hum Genet. 2015 Nov;60(11):703-8. doi: 10.1038/jhg.2015.64. Epub 2015 Jun 4.

Functional and genetic diversity of leukocyte immunoglobulin-like receptor and implication for disease associations.

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Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.


Human leukocyte immunoglobulin-like receptors (LILR) are a family of 11 functional genes encoding five activating (LILRA1, 2, 4-6), five inhibitory (LILRB1-5) and one soluble (LILRA3) form. The number of LILR genes is conserved among individuals, except for LILRA3 and LILRA6, which exhibit copy-number variations. The LILR genes are rapidly evolving and showing large interspecies differences, making it difficult to analyze the functions of LILR using an animal model. LILRs are expressed on various cells such as lymphoid and myeloid cells and the expression patterns are different from gene to gene. The LILR gene expression and polymorphisms have been reported to be associated with autoimmune and infectious diseases such as rheumatoid arthritis and cytomegalovirus infection. Although human leukocyte antigen (HLA) class I is a well-characterized ligand for some LILRs, non-HLA ligands have been increasingly identified in recent years. LILRs have diverse functions, including the regulation of inflammation, immune tolerance, cell differentiation and nervous system plasticity. This review focuses on the genetic and functional diversity of the LILR family.

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