ICOSLG

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ICOSLG
Identifiers
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
RefSeq (mRNA)

NM_015790

RefSeq (protein)

NP_001269979
NP_001269980
NP_001269981
NP_056074
NP_001352688

NP_056605

Location (UCSC)Chr 21: 44.22 – 44.24 MbChr 10: 77.91 – 77.92 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

ICOS ligand is a protein that in humans is encoded by the ICOSLG gene[5][6][7] located at chromosome 21. ICOSLG has also been designated as CD275 (cluster of differentiation 275).

ICOSLG is glycosylated transmembrane structure, which is classified as a member of the

immunocytes in immune responses
.

The interaction of ICOSLG with ICOS, the specific receptor for ICOSLG, is critically involved in the activation, proliferation, differentiation and cytokine production of T cells as well as in the antibody secretion from B cells during secondary immune responses.[8]

ICOSLG, which is extensively expressed in both non-lymphatic and

Th2 cytokines and thus shifts the immune response to the Th2 type. It has been reported that the ICOS/ICOSLG pathway is involved in immunopathogenesis such as infection, hypersensitivity, autoimmune diseases
, transplantation immunity and tumor immunity.

ICOSLG is also a major

endothelial cell-mediated T cell activation. It has an important physiological role of ICOSLG in the reactivation of effector/memory T cells on the endothelium controlling the entry of immune cells into inflamed tissue.[9]

Structure

Inducible costimulator-ligand (ICOS-L) is a member of the B7 family of costimulatory ligands

splice variants of human ICOSLG have been described and designated hICOSLG and B7-H2/B7RP-1/hLICOS.[11]

Both molecules have an identical

carboxyl-terminal end of their cytoplasmic regions. In humans, cell surface expression of ICOSLG has been described on B cells, dendritic cells, monocytes/macrophages, and T cells. In addition, mRNA expression of ICOSLG has been detected in a variety of lymphoid and nonlymphoid organs, with hICOSLG showing a more lymphoid-restricted expression pattern (spleen, lymph node), whereas B7-H2/B7RP-1/hLICOSmRNA was expressed in all organs examined (e.g., spleen, kidney, heart, and brain).[12]

Interaction

Murine ICOSLG, unlike

CTLA-4.[13] In humans, ICOSLG binds to ICOS but also to CD28 and CTLA-4.[14]

The strong impact of ICOS/ICOSLG interaction on T cell-mediated immune responses in vivo became evident by the disruption of the ICOS gene in mice. ICOS deficient mice are characterized by impaired germinal center formation, have a profound defect in

experimental allergic encephalomyelitis and of cardiac allograft rejection revealed a critical role of ICOS and its ligand in inflammatory immune reactions.[9]

Immunodeficiencies

The research with mutant ICOSLG showed that if the protein was retained in ER/GA, instead of the cell surface in normal case, it diminished B cell costimulation of T cells. It led to defect in antibody and memory B cell generation. Mutant ICOSLG also impaired migration of lymphocytes and neutrophils across endothelial cells, which normally express ICOSLG. These defects contributed with altered adaptive immunity and neutropenia in patient, thus showing ICOSLG deficiency as a cause of combined immunodeficiency.[15]

Immunotherapy

The fluctuant balance between co-stimulatory and coinhibitory signals that a T cell receives participates in the initiation, effection, and termination of an immune response. Excessive activation and immune reaction of T cells may result in autoimmune diseases and host immune injury.

ICOSLG delivers a potent co-stimulatory signal to T cells when engaged by ICOS, resulting in T cell activation and proliferation. The existence of ICOS/ICOSLG signal in vivo is closely associated with many mouse autoimmune disease models. Conversely, the absence of ICOS/ICOSLG signal may be a good way to relieve autoimmune disease. In view of its critical function in regulating immunohomeostasis, ICOS signaling has aroused great attention in immunodiagnosis and therapy.[8]

The ICOS/ICOSLG axis has been shown to promote either antitumor T cell responses (when activated in Th1 and other Teff) or protumor responses when triggered in

monoclonal antibodies (mAbs) targeting this pathway are being investigated for cancer immunotherapy.[16]Stimulation of the ICOS pathway by tumor cell vaccine expressing ICOSLG, in combination with anti-CTLA-4 therapy blockade, led to enhanced antitumor efficacy. This combined treatment approach, which integrates ICOS costimulation through ICOSLG and CTLA-4 blockade, effectively alters tumor-associated macrophages (TAMs) towards a phenotype that fights against tumors, showing significant promise for cancer treatment.[17]

Undoubtedly, the development of more efficient and specific monoclonal antibodies may be important for further disclosure of ICOSLG function. Agonistic Abs are currently being administered either alone or in combination with immunotherapy and chemotherapy.[18]

References list

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000160223 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000732 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. PMID 9734811
    .
  6. .
  7. ^ "Entrez Gene: ICOSLG inducible T-cell co-stimulator ligand".
  8. ^
    PMID 21851236
    .
  9. ^ .
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  11. PMID 11023515.{{cite journal}}: CS1 maint: DOI inactive as of March 2024 (link
    )
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Further reading

External links

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