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Beschreibung

Inducible T-cell costimulator (UniProt Q9WVS0, also known as Activation-inducible lymphocyte immunomediatory molecule, CCLP, CD278, CD28 and CTLA-4-like protein, CD28-related protein 1, CRP-1, H4) is encoded by the Icos (also known as Ailim) gene (Gene ID 54167) in murine species. ICOS is a costimulatory molecule expressed on activated T cells and regulatory T cells, it plays a crucial role in T-cell survival and function, Th2 cell differentiation, and lung inflammatory responses. Upon ICOS-ligand (ICOS-L) binding, ICOS initiates a cascade of intracellular signaling events, leading to the production of cytokines such as IL-4 and IL-13. Both ICOS and ICOS-L are expressed on type 2 innate lymphoid cells (ILC2s) that, along with Th2 cells, contribute to the pathogenesis of asthma by producing copious amounts of IL-5 and IL-13. ICOS and ICOS-L interaction is reported to promote cytokine production and survival of ILC2s through STAT5 signaling. ICOS-deficiency or blocking ICOS and ICOS-L interaction is shown to prevent cytokine-induced asthma and lung inflammation in a humanized murine model with adoptively transferred human peripheral ILC2s. Human and murine ICOS proteins are produced with a signal peptide (a.a. 1-20) sequence, which is removed posttranslationally to yield the mature protein with a large N-terminal extracellular (human a.a. 21-140 and murine a.a. 21-144) region composed almost entirely of a V-type Ig-like domain (human a.a. 30-132 and murine a.a. 30-133), followed by a transmembrane domain (human a.a. 141-161 and murine a.a. 145-165) and a cytoplasmic tail (human a.a. 162-199 and murine a.a. 166-200).