LILRA6 copy number variation correlates with susceptibility to atopic dermatitis

Abstract

Leukocyte immunoglobulin-like receptors (LILR) are expressed mostly on myelomonocytic cells where they are mediators of immunological tolerance. Two LILR genes, LILRA3 and LILRA6, exhibit marked copy number variation. We assessed the contribution of these genes to atopic dermatitis (AD) by analysing transmission in 378 AD families. The data indicated that copies of LILRA6 were over-transmitted to affected patients. They are consistent with a contribution of LILR genes to AD. They could affect the equilibrium between activating and inhibitory signals in the immune response.

Keratinocyte Proline-Rich Protein Deficiency in Atopic Dermatitis Leads to Barrier Disruption

“…With regard to AD, CNV within FLG is reported to make a significant, dose-dependent contribution to the risk of disease development. CNVs of some other genes have been also reported (Chen et al, 2013;Li et al, 2016;Lopez-Alvarez et al, 2016). Here, we performed allelotyping analysis in AD patients in Japan to discover uncharacterized genetic factors for AD.…”

qKAT: a high-throughput qPCR method for KIR gene copy number and haplotype determination

“…KIR A/B haplotype-defining genes). To date, 21 published studies (comprising >20,000 samples in total) including investigations of KIR disease association, function, expression and imputation have utilised the method [ 13 , 31 , 34 , 38 , 43 , 45 – 60 ]. A KIR typing service using qKAT has also been established at the Addenbrooke’s Hospital Histocompatibility and Immunogenetics (Tissue Typing) laboratory in Cambridge (UK).…”

Leukocyte Immunoglobulin-Like Receptors A2 and A6 are Expressed in Avian Macrophages and Modulate Cytokine Production by Activating Multiple Signaling Pathways

“…Based on the interaction with human leukocyte antigen (HLA) class I molecules, human LILRAs are categorized into LILRA group 1 (LILRA1–3) and LILRA group 2 (LILRA4–6) members [ 7 , 10 ]. Moreover, LILRAs have been demonstrated to play important roles in infection or autoimmune diseases such as HIV infection [ 11 ], multiple sclerosis [ 12 ], atopic dermatitis [ 13 ] and rheumatoid arthritis [ 14 ]. It has been reported that LILRA1, 3, 4 and 5 bind with HLA-G, HLA-C and classical HLAs [ 3 , 7 , 11 , 13 , 14 ] and regulate adaptive or innate immune pathways such as the ERK/MEK [ 15 ], TLR [ 3 ] and JNK/p38MAPK [ 16 ] signaling pathways.…”

“…Moreover, LILRAs have been demonstrated to play important roles in infection or autoimmune diseases such as HIV infection [ 11 ], multiple sclerosis [ 12 ], atopic dermatitis [ 13 ] and rheumatoid arthritis [ 14 ]. It has been reported that LILRA1, 3, 4 and 5 bind with HLA-G, HLA-C and classical HLAs [ 3 , 7 , 11 , 13 , 14 ] and regulate adaptive or innate immune pathways such as the ERK/MEK [ 15 ], TLR [ 3 ] and JNK/p38MAPK [ 16 ] signaling pathways. Additionally, they have been reported to upregulate the cytokines IL-1R, IL-4, IL-6, IL-10, IL-12, IL-17, TNFα and IFN-γ [ 3 , 7 , 11 , 14 ].…”

“…In humans, LILRA2 is a type of innate immune receptor in the host immune system that plays a role in the immune response to microbial pathogens such as Mycoplasma hyorhinis , Streptococcus pneumonia , Candida albicans and Legionella pneumophila [ 1 ] and conditions such as inflammatory bowel disease [ 17 ] and rheumatoid arthritis [ 18 ]. In addition, human LILRA6 is correlated with susceptibility to atopic dermatitis [ 13 ]. Cross-linking of LILRA2 and LILRA6 on the surface of macrophages induces and regulates cytokines such as IL-4, IL-10, IL-17, TNFα and IFN-γ [ 3 , 6 , 9 ].…”