LILRB4 explained

Leukocyte immunoglobulin-like receptor subfamily B member 4 is a protein that in humans is encoded by the LILRB4 gene.^{[1] [2] [3]}

This gene is a member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein belongs to the subfamily B class of LIR receptors which contain two or four extracellular immunoglobulin domains, a transmembrane domain, and two to four cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The receptor is expressed on monocytic cells and transduces a negative signal that inhibits stimulation of an immune response. The receptor can also function in antigen capture and presentation. It is thought to control inflammatory responses and cytotoxicity to help focus the immune response and limit autoreactivity. LILRB4 has also been proposed to be a potential target for tumor immunotherapy. It has been shown to express on tumor-associated macrophages and negatively regulate immune response in tumor.^[4] The expression of LILRB4 on monocytic myeloid leukemia cells supports infiltration and inhibits T cell proliferation. Multiple transcript variants encoding different isoforms have been found for this gene.

Interactions

LILRB4 has been shown to interact with PTPN6^[5] and INPP5D (SHIP-1).^[6]

See also

• Cluster of differentiation
• Immunoglobulin superfamily

Further reading

• Deng M, Gui X, Kim J, Xie L, Chen W, Li Z, He L, Chen Y, Chen H, Luo W, Lu Z, Xie J, Churchill H, Xu Y, Zhou Z, Wu G, Yu C, John S, Hirayasu K, Nguyen N, Liu X, Huang F, Li L, Deng H, Tang H, Sadek AH, Zhang L, Huang T, Zou Y, Chen B, Zhu H, Arase H, Xia N, Jiang Y, Collins R, You MJ, Homsi J, Unni N, Lewis C, Chen GQ, Fu YX, Liao XC, An Z, Zheng J, Zhang N, Zhang CC . 6 . LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration . Nature . 562 . 7728 . 605–609 . October 2018 . 30333625 . 6296374 . 10.1038/s41586-018-0615-z . 2018Natur.562..605D .
• John S, Chen H, Deng M, Gui X, Wu G, Chen W, Li Z, Zhang N, An Z, Zhang CC . A Novel Anti-LILRB4 CAR-T Cell for the Treatment of Monocytic AML . Molecular Therapy . 26 . 10 . 2487–2495 . October 2018 . 30131301 . 6171100 . 10.1016/j.ymthe.2018.08.001 .
• Gui X, Deng M, Song H, Chen Y, Xie J, Li Z, He L, Huang F, Xu Y, Anami Y, Yu H, Yu C, Li L, Yuan Z, Xu X, Wang Q, Chai Y, Huang T, Shi Y, Tsuchikama K, Liao XC, Xia N, Gao GF, Zhang N, Zhang CC, An Z . 6 . Disrupting LILRB4/APOE Interaction by an Efficacious Humanized Antibody Reverses T-cell Suppression and Blocks AML Development . Cancer Immunology Research . 7 . 8 . 1244–1257 . August 2019 . 31213474 . 6677629 . 10.1158/2326-6066.CIR-19-0036 .
• Suciu-Foca N, Cortesini R . Central role of ILT3 in the T suppressor cell cascade . Cellular Immunology . 248 . 1 . 59–67 . July 2007 . 17923119 . 10.1016/j.cellimm.2007.01.013 .
• Arm JP, Nwankwo C, Austen KF . Molecular identification of a novel family of human Ig superfamily members that possess immunoreceptor tyrosine-based inhibition motifs and homology to the mouse gp49B1 inhibitory receptor . Journal of Immunology . 159 . 5 . 2342–9 . September 1997 . 10.4049/jimmunol.159.5.2342 . 9278324 .
• Kuroiwa A, Yamashita Y, Inui M, Yuasa T, Ono M, Nagabukuro A, Matsuda Y, Takai T . 6 . Association of tyrosine phosphatases SHP-1 and SHP-2, inositol 5-phosphatase SHIP with gp49B1, and chromosomal assignment of the gene . The Journal of Biological Chemistry . 273 . 2 . 1070–4 . January 1998 . 9422771 . 10.1074/jbc.273.2.1070 . free .
• Borges L, Hsu ML, Fanger N, Kubin M, Cosman D . A family of human lymphoid and myeloid Ig-like receptors, some of which bind to MHC class I molecules . Journal of Immunology . 159 . 11 . 5192–6 . December 1997 . 10.4049/jimmunol.159.11.5192 . 9548455 .
• Torkar M, Norgate Z, Colonna M, Trowsdale J, Wilson MJ . Isotypic variation of novel immunoglobulin-like transcript/killer cell inhibitory receptor loci in the leukocyte receptor complex . European Journal of Immunology . 28 . 12 . 3959–67 . December 1998 . 9862332 . 10.1002/(SICI)1521-4141(199812)28:12<3959::AID-IMMU3959>3.0.CO;2-2 . free .
• Wang LL, Blasioli J, Plas DR, Thomas ML, Yokoyama WM . Specificity of the SH2 domains of SHP-1 in the interaction with the immunoreceptor tyrosine-based inhibitory motif-bearing receptor gp49B . Journal of Immunology . 162 . 3 . 1318–23 . February 1999 . 10.4049/jimmunol.162.3.1318 . 9973385 .
• Wilson MJ, Torkar M, Haude A, Milne S, Jones T, Sheer D, Beck S, Trowsdale J . 6 . Plasticity in the organization and sequences of human KIR/ILT gene families . Proceedings of the National Academy of Sciences of the United States of America . 97 . 9 . 4778–83 . April 2000 . 10781084 . 18309 . 10.1073/pnas.080588597 . 2000PNAS...97.4778W . free .
• Heinzmann A, Blattmann S, Forster J, Kuehr J, Deichmann KA . Common polymorphisms and alternative splicing in the ILT3 gene are not associated with atopy . European Journal of Immunogenetics . 27 . 3 . 121–7 . June 2000 . 10940079 . 10.1046/j.1365-2370.2000.00214.x .
• Liu WR, Kim J, Nwankwo C, Ashworth LK, Arm JP . Genomic organization of the human leukocyte immunoglobulin-like receptors within the leukocyte receptor complex on chromosome 19q13.4 . Immunogenetics . 51 . 8–9 . 659–69 . July 2000 . 10941837 . 10.1007/s002510000183 . 23687483 .
• Young NT, Canavez F, Uhrberg M, Shum BP, Parham P . Conserved organization of the ILT/LIR gene family within the polymorphic human leukocyte receptor complex . Immunogenetics . 53 . 4 . 270–8 . 2001 . 11491530 . 10.1007/s002510100332 . 2819935 .
• Chang CC, Ciubotariu R, Manavalan JS, Yuan J, Colovai AI, Piazza F, Lederman S, Colonna M, Cortesini R, Dalla-Favera R, Suciu-Foca N . 6 . Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4 . Nature Immunology . 3 . 3 . 237–43 . March 2002 . 11875462 . 10.1038/ni760 . 35400503 .
• LeMaoult J, Zafaranloo K, Le Danff C, Carosella ED . HLA-G up-regulates ILT2, ILT3, ILT4, and KIR2DL4 in antigen presenting cells, NK cells, and T cells . FASEB Journal . 19 . 6 . 662–4 . April 2005 . 15670976 . 10.1096/fj.04-1617fje . free . 24608530 .
• Garner LI, Salim M, Mohammed F, Willcox BE . Expression, purification, and refolding of the myeloid inhibitory receptor leukocyte immunoglobulin-like receptor-5 for structural and ligand identification studies . Protein Expression and Purification . 47 . 2 . 490–7 . June 2006 . 16406677 . 10.1016/j.pep.2005.11.020 .
• Kim-Schulze S, Seki T, Vlad G, Scotto L, Fan J, Colombo PC, Liu J, Cortesini R, Suciu-Foca N . 6 . Regulation of ILT3 gene expression by processing of precursor transcripts in human endothelial cells . American Journal of Transplantation . 6 . 1 . 76–82 . January 2006 . 16433759 . 10.1111/j.1600-6143.2005.01162.x . 7662795 . free .
• Kim-Schulze S, Scotto L, Vlad G, Piazza F, Lin H, Liu Z, Cortesini R, Suciu-Foca N . 6 . Recombinant Ig-like transcript 3-Fc modulates T cell responses via induction of Th anergy and differentiation of CD8+ T suppressor cells . Journal of Immunology . 176 . 5 . 2790–8 . March 2006 . 16493035 . 10.4049/jimmunol.176.5.2790 . free .
• Vlad G, Liu Z, Zhang QY, Cortesini R, Suciu-Foca N . Immunosuppressive activity of recombinant ILT3 . International Immunopharmacology . 6 . 13–14 . 1889–94 . December 2006 . 17161342 . 10.1016/j.intimp.2006.07.017 .

Notes and References

1. Cella M, Döhring C, Samaridis J, Dessing M, Brockhaus M, Lanzavecchia A, Colonna M . A novel inhibitory receptor (ILT3) expressed on monocytes, macrophages, and dendritic cells involved in antigen processing . The Journal of Experimental Medicine . 185 . 10 . 1743–51 . May 1997 . 9151699 . 2196312 . 10.1084/jem.185.10.1743 .
2. Samaridis J, Colonna M . Cloning of novel immunoglobulin superfamily receptors expressed on human myeloid and lymphoid cells: structural evidence for new stimulatory and inhibitory pathways . European Journal of Immunology . 27 . 3 . 660–5 . March 1997 . 9079806 . 10.1002/eji.1830270313 . 2212182 . free .
3. Web site: Entrez Gene: LILRB4 leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 4.
4. Sharma N, Atolagbe OT, Ge Z, Allison JP . LILRB4 suppresses immunity in solid tumors and is a potential target for immunotherapy . The Journal of Experimental Medicine . 218 . 7 . July 2021 . 33974041 . 8117208 . 10.1084/jem.20201811 .
5. Wang LL, Blasioli J, Plas DR, Thomas ML, Yokoyama WM . Specificity of the SH2 domains of SHP-1 in the interaction with the immunoreceptor tyrosine-based inhibitory motif-bearing receptor gp49B . Journal of Immunology . 162 . 3 . 1318–23 . February 1999 . 10.4049/jimmunol.162.3.1318 . 9973385 .
6. Zurli V, Wimmer G, Cattaneo F, Candi V, Cencini E, Gozzetti A, Raspadori D, Campoccia G, Sanseviero F, Bocchia M, Baldari CT, Kabanova A . 6 . Ectopic ILT3 controls BCR-dependent activation of Akt in B-cell chronic lymphocytic leukemia . Blood . 130 . 18 . 2006–2017 . November 2017 . 28931525 . 10.1182/blood-2017-03-775858 . free .