RGMB enhances the suppressive activity of the monomeric secreted form of CTLA-4.

RGMB enhances the suppressive activity of the monomeric secreted form of CTLA-4.

Publication date: May 06, 2019

The immunoregulatory molecule CTLA-4 plays a crucial role in the maintenance of immune homeostasis. CTLA-4-neutralizing antibodies are now approved for the treatment of advanced melanoma, and are in development for treating other cancers as well. However, a thorough understanding of CTLA-4 function at the molecular level is necessary in order to develop strategies to prevent the unintended autoimmunity that is frequently associated with systemic blockade of CTLA-4 activity. Here, we describe an extracellular molecule, repulsive guidance molecule B (RGMB) as a novel binding partner of CTLA-4. RGMB expression was detected at high levels in dendritic cell subsets that have been suggested to have tolerogenic capabilities. RGMB binds an extracellular domain of CTLA-4, and specifically strengthens the binding of the monomeric, soluble form of CTLA-4 (sCTLA-4) to CD80, enhancing CTLA-4’s suppressive effect on co-stimulation. Examination of expression data from tumor tissues revealed a negative correlation between RGMB expression and immune activation status in the majority of non-hematologic tumor tissues. These findings advance our understanding of CTLA-4 activity, as well as identify the RGMB/CTLA-4 binding interface as a potential target for the development of novel immune checkpoint blockade therapies.

Open Access PDF

Sekiya, T. and Takaki, S. RGMB enhances the suppressive activity of the monomeric secreted form of CTLA-4. 22540. 2019 Sci Rep (9):1.

Concepts Keywords
Antibodies Antibodies
Autoimmunity B7
Blockade CTLA-4
CD80 Bristol-Myers Squibb
Correlation T cells
Extracellular Immune checkpoint
Homeostasis Checkpoint inhibitor
Immune Checkpoint Blockade Receptors
Melanoma Branches of biology
Molecule Organ systems
Sci Medicine
Tumor Immune system
Melanoma
Cancers
Non hematologic tumor
Tissues Tumor
Melanoma treating

Semantics

Type Source Name
pathway BSID Reproduction
gene UNIPROT AICDA
gene UNIPROT DUOXA1
gene UNIPROT CD1C
gene UNIPROT CPSF4
gene UNIPROT FOXP3
gene UNIPROT CD36
gene UNIPROT FAT1
drug DRUGBANK Palmitic Acid
disease DOID Allergy
disease MESH Allergy
gene UNIPROT GATA3
gene UNIPROT PTGDR
gene UNIPROT ELAVL2
drug DRUGBANK Huperzine B
disease DOID encephalomyelitis
disease MESH encephalomyelitis
disease MESH diffuse cutaneous systemic sclerosis
disease DOID myasthenia gravis
disease MESH myasthenia gravis
pathway BSID Autoimmune thyroid disease
pathway BSID Systemic lupus erythematosus
disease DOID systemic lupus erythematosus
disease MESH systemic lupus erythematosus
gene UNIPROT BRD2
disease DOID psoriasis
disease MESH psoriasis
drug DRUGBANK Ipilimumab
drug DRUGBANK Abatacept
gene UNIPROT MBNL1
gene UNIPROT COL9A3
gene UNIPROT COMP
gene UNIPROT COL9A1
gene UNIPROT COL9A2
gene UNIPROT SCN8A
gene UNIPROT EXOG
disease DOID autoimmune disease
disease MESH Lymphoproliferative disorders
gene UNIPROT CTBP1
gene UNIPROT PRDM6
disease MESH infection
gene UNIPROT LAMC2
gene UNIPROT CSF2
gene UNIPROT CD4
drug DRUGBANK Esomeprazole
gene UNIPROT KIT
gene UNIPROT SET
gene UNIPROT FBXO8
gene UNIPROT FBRS
gene UNIPROT TRIM27
drug DRUGBANK Rifampicin
gene UNIPROT THY1
gene UNIPROT STPG4
gene UNIPROT CCL21
drug DRUGBANK Methylergometrine
disease MESH separated
drug DRUGBANK Edetic Acid
gene UNIPROT WASHC1
gene UNIPROT MIXL1
drug DRUGBANK Tromethamine
drug DRUGBANK Glycine
drug DRUGBANK Imidazole
gene UNIPROT TSPO
gene UNIPROT CHRM3
gene UNIPROT C2
drug DRUGBANK Isopropyl beta-D-thiogalactopyranoside
gene UNIPROT GAL
drug DRUGBANK L-Leucine
drug DRUGBANK L-Tryptophan
disease MESH tryptophan
drug DRUGBANK Gold
disease DOID ORF
gene UNIPROT ITGAX
gene UNIPROT PROC
gene UNIPROT APC
gene UNIPROT MBL2
gene UNIPROT PHGDH
gene UNIPROT SSRP1
gene UNIPROT HPRT1
disease DOID cancer
gene UNIPROT SLC25A16
disease DOID thyroid carcinoma
disease MESH thyroid carcinoma
gene UNIPROT OAT
gene UNIPROT GAPDH
gene UNIPROT SDS
gene UNIPROT SBDS
drug DRUGBANK Sodium lauryl sulfate
gene UNIPROT RPS3A
gene UNIPROT NR3C2
disease MESH multiple
gene UNIPROT CD8A
gene UNIPROT TLR1
gene UNIPROT OCA2
gene UNIPROT B3GALNT1
drug DRUGBANK Proline
disease MESH **p
gene UNIPROT SRA1
gene UNIPROT APBB3
gene UNIPROT MSR1
gene UNIPROT NOVA2
gene UNIPROT GZMB
gene UNIPROT PRF1
gene UNIPROT ZNF395
pathway BSID Rheumatoid arthritis
disease DOID rheumatoid arthritis
disease MESH rheumatoid arthritis
gene UNIPROT SOD1
gene UNIPROT ZNF10
disease DOID lymphoma
disease MESH lymphoma
gene UNIPROT MENT
drug DRUGBANK Trestolone
gene UNIPROT DYRK3
gene UNIPROT IK
gene UNIPROT ECD
gene UNIPROT SEM1
disease DOID ECD
gene UNIPROT ADAM11
gene UNIPROT CCL22
drug DRUGBANK BK-MDA
disease DOID Hfe2
gene UNIPROT BTG3
drug DRUGBANK Cycloserine
gene UNIPROT APCS
drug DRUGBANK Amino acids
gene UNIPROT DEPP1
gene UNIPROT GOPC
gene UNIPROT GSTK1
gene UNIPROT SLCO6A1
drug DRUGBANK Glutathione
gene UNIPROT TNF
gene UNIPROT RABGEF1
gene UNIPROT RAP1A
gene UNIPROT TERF2IP
gene UNIPROT IRF6
gene UNIPROT HJV
gene UNIPROT GNPDA1
gene UNIPROT GPI
gene UNIPROT RGMA
gene UNIPROT CEP55
disease DOID hepatitis
disease MESH hepatitis
disease DOID dermatitis
disease MESH dermatitis
disease DOID colitis
disease MESH colitis
disease MESH autoimmune diseases
gene UNIPROT CD86
disease MESH suffering
disease MESH repression
gene UNIPROT CD28
drug DRUGBANK Coenzyme M
gene UNIPROT CD80
disease MESH autoimmunity
disease MESH cancers
disease MESH development
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
gene UNIPROT CTLA4
gene UNIPROT RGMB

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