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FLASH GENE

Symbol

ICOSLG

contributors: mct - updated : 02-01-2017

HGNC name	inducible T-cell co-stimulator ligand
HGNC id	17087

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001283050 7 - 1188 NP_001269979 - 309 - 2000 11023515 NM_001283051 6 - 2969 NP_001269980 - 185 - 2000 11023515 NM_001283052 7 - 3168 NP_001269981 - 217 - 2000 11023515 NM_015259 7 - 3320 NP_056074 - 302 - 2000 11023515

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive liver         Nervous brain         Urinary kidney

cells

System Cell Pubmed Species Stage Rna symbol Respiratory epithelial cell Urinary tubular cell

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	one Ig-like C2-type (immunoglobulin-like) domain
	one Ig-like V-type (immunoglobulin-like) domain

conjugated

GlycoP

HOMOLOGY

Homologene

FAMILY	immunoglobulin superfamily, BTN/MOG family
	B7 superfamily

CATEGORY

signaling

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane

basic FUNCTION	acting as a costimulatory signal for T-cell proliferation and cytokine secretion
	inducing also B-cell proliferation and differentiation into plasma cells
	may play an important role in mediating local tissue responses to inflammatory conditions, as well as in modulating the secondary immune response by co-stimulating memory T-cell function
	may facilitate progression of acute myeloid leukemia
	ICOS-ICOSLG signal plays a direct role in proliferation and differentiation of thyroid follicular cells (TFC) and may exert important effects in the initiation, maintenance and exaggeration of autoimmune responses in local tissue
	ICOS/ICOSLG interaction is a central event in immunosuppression of tumor-associated memory CD4(+) T cells
	ICOSLG blockade abrogates likely tolerance at the fetomaternal interface by enhancing CD8(+) effector response and reducing local immunomodulation mediated by CD8(+) regulatory T cells
	potential functional link between ADAM17 and ICOSLG in controlling adaptive immune responses
	beyond the role in promoting T-helper (TFH) cells development, ICOSLG is important for individual B cells to competitively participate in the germinal centre (GC) reaction and to develop into bone-marrow plasma cells (BMPCs)
	may participate in antigen presentation by epithelial cells
	plays a critical role in immune response

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

immunity/defense

text	positive regulation of activated T cell proliferation

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein	ICOSLG-CD28 interaction was essential for the costimulation of human T cells primary responses to allogeneic antigens and memory recall responses
	TNFRSF13 negatively regulates ICOSLG expression on B cells
	loss of TNFRSF13B leads to increased ICOSLG expression and expands T follicular helper (Tfh) and germinal center (GC) B cells

cell & other

REGULATION

Other

up-regulated by TNF-alpha

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in patients with systemic lupus erythematosus constitutional     --over   of ICOS and ICOSLG in Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and vasculitic neuropathy (VN) vs patients with hereditary neuropathies (HNs)

Susceptibility

to Crohn disease

Variant & Polymorphism other	rs7282490 ICOSLG GG risk carriers associated with an ileal Crohn disease phenotype

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

Icosl -/- mice are healthy and fertile but have a reduced IgG1 production and affinity maturation, indicating a defect in T cell responses. Also have impaired T and B-cell interaction and germinal center formation