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immunoglobulin like domain containing receptor 2

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2986

Nomenclature: immunoglobulin like domain containing receptor 2

Abbreviated Name: ILDR2

Family: Other immune checkpoint proteins

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 639 1q24.1 ILDR2 immunoglobulin like domain containing receptor 2
Mouse 1 661 1 H2.3; 1 73.61 cM Ildr2 immunoglobulin-like domain containing receptor 2
Rat - - 13q23 Ildr2 immunoglobulin-like domain containing receptor 2
Previous and Unofficial Names Click here for help
immunoglobulin-like domain containing receptor 2 | LISCH-like (mouse)
Database Links Click here for help
Alphafold
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Immunopharmacology Comments
ILDR2 has been identified as a novel inhibitory T cell immune checkpoint protein that belongs to the B7-like protein family [2]. It exhibits negative regulatory effects on human and mouse T cells in a number of experimental systems. Its counterpart receptor expressed on activated T cells has not been definitively identified. ILDR2 expression in increased in patient-derived inflamed tissues (samples from ulcerative colitis and Crohn's disease patients). An ILDR2-Fc fusion protein ameliorates disease markers of rheumatoid arthritis in the collagen-induced arthritis mouse model, and in the multiple sclerosis EAE model [6] indicating the potential for pharmacological intervention at this novel immune checkpoint. Bayer are developing their anti-ILDR2 antibody BAY1905254 for immuno-oncology potential (see Phase 1 study NCT03666273). BAY1905254 enhances antigen-specific T cell proliferation and cytotoxicity, and anti-tumour activity has been observed in preclinical studies [4].
General Comments
ILDR2 is one of a family of three 'angulin' proteins [5]: angulin-1 (LSR), angulin-2 (ILDR1) and angulin-3 (ILDR2). The angulins are involved in tricellulin recruitment and formation of tricellular tight-gap junctions that are important to the maintenance of epithelial barrier integrity [1,3,7-8].

References

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1. Furuse M, Izumi Y, Oda Y, Higashi T, Iwamoto N. (2014) Molecular organization of tricellular tight junctions. Tissue Barriers, 2: e28960. [PMID:25097825]

2. Hecht I, Toporik A, Podojil JR, Vaknin I, Cojocaru G, Oren A, Aizman E, Liang SC, Leung L, Dicken Y et al.. (2018) ILDR2 Is a Novel B7-like Protein That Negatively Regulates T Cell Responses. J Immunol, 200 (6): 2025-2037. [PMID:29431694]

3. Higashi T, Tokuda S, Kitajiri S, Masuda S, Nakamura H, Oda Y, Furuse M. (2013) Analysis of the 'angulin' proteins LSR, ILDR1 and ILDR2--tricellulin recruitment, epithelial barrier function and implication in deafness pathogenesis. J Cell Sci, 126 (Pt 4): 966-77. [PMID:23239027]

4. Huetter J, Gritzan U, Gutcher I, Golfier S, Doecke W-D, Leutke-Eversloh MV, Roider H, Hunter J, Pow A, Liang S et al.. (2018) Abstract 2778: Discovery and preclinical characterization of BAY 1905254 a novel immune checkpoint inhibitor for cancer immunotherapy targeting the immunoglobulin-like domain containing receptor 2 (ILDR2). Cancer Research, 78 (13 (Supplement)). DOI: 10.1158/1538-7445.AM2018-2778

5. Liu Y, Nie H, Liu C, Zhai X, Sang Q, Wang Y, Shi D, Wang L, Xu Z. (2017) Angulin proteins ILDR1 and ILDR2 regulate alternative pre-mRNA splicing through binding to splicing factors TRA2A, TRA2B, or SRSF1. Sci Rep, 7 (1): 7466. [PMID:28785060]

6. Podojil JR, Hecht I, Chiang MY, Vaknin I, Barbiro I, Novik A, Neria E, Rotman G, Miller SD. (2018) ILDR2-Fc Is a Novel Regulator of Immune Homeostasis and Inducer of Antigen-Specific Immune Tolerance. J Immunol, 200 (6): 2013-2024. [PMID:29431690]

7. Sohet F, Lin C, Munji RN, Lee SY, Ruderisch N, Soung A, Arnold TD, Derugin N, Vexler ZS, Yen FT et al.. (2015) LSR/angulin-1 is a tricellular tight junction protein involved in blood-brain barrier formation. J Cell Biol, 208 (6): 703-11. [PMID:25753034]

8. Watanabe K, Watson E, Cremona ML, Millings EJ, Lefkowitch JH, Fischer SG, LeDuc CA, Leibel RL. (2013) ILDR2: an endoplasmic reticulum resident molecule mediating hepatic lipid homeostasis. PLoS ONE, 8 (6): e67234. [PMID:23826244]

How to cite this page

Other immune checkpoint proteins: immunoglobulin like domain containing receptor 2. Last modified on 04/04/2019. Accessed on 23/02/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2986.