Type II cytokine receptor explained

Type II cytokine receptors, also commonly known as class II cytokine receptors, are transmembrane proteins that are expressed on the surface of certain cells. They bind and respond to a select group of cytokines including interferon type I, interferon type II, interferon type III.[1] and members of the interleukin-10 family These receptors are characterized by the lack of a WSXWS motif which differentiates them from type I cytokine receptors.[2]

Structure

Typically type II cytokine receptors are heterodimers or multimers with a high and a low affinity component. These receptors are related predominantly by sequence similarities in their extracellular portions that are composed of tandem Ig-like domains. The structures for the extracellular domains of the receptors for interferon types, I, II, and III are all known.[3]

Type II cytokine receptors are tyrosine-kinase-linked receptors. The intracellular domain of type II cytokine receptors is typically associated with a tyrosine kinase belonging to the Janus kinase (JAK family). Binding of the receptor typically leads to activation of the canonical JAK/STAT signaling pathway.[4]

Types

Type II cytokine receptors include those that bind interferons and those that bind members of the interleukin-10 family (interleukin-10, interleukin-20, interleukin-22, and interleukin-28).[5] [6] Expression of specific receptor varieties is highly variable across tissue types with some receptors being ubiquitously expressed and some receptors only expressed in specific tissues.

Interferon receptors

The interferon receptor is a molecule displayed on the surface of cells which interacts with extracellular interferons. Class II cytokine receptors bind type I, type II, and type III interferons. Type I interferons play important roles in both the adaptive and innate immune responses, prevent proliferation of pathogens, and have antiviral activities. Type II interferons help to modulate the immune system’s response to pathogens, and these interferons also respond to pathogens. Type III interferons induce a similar response to type I interferons, but their expression is limited to epithelial cells. The receptor is coded for by number of different genes, due to the diversity of types of interferons. Regulation of cell surface receptor levels plays an important role in the regulation and limiting of interferon signaling.

Interleukin receptors

Notes and References

  1. Krey K, Babnis AW, Pichlmair A . System-Based Approaches to Delineate the Antiviral Innate Immune Landscape . Viruses . 12 . 10 . 1196 . October 2020 . 33096788 . 10.3390/v12101196 . 7589202 . free .
  2. Stanifer ML, Pervolaraki K, Boulant S . Differential Regulation of Type I and Type III Interferon Signaling . International Journal of Molecular Sciences . 20 . 6 . March 2019 . 1445 . 30901970 . 6471306 . 10.3390/ijms20061445 . free .
  3. Walter MR . The Role of Structure in the Biology of Interferon Signaling . Frontiers in Immunology . 11 . 606489 . 2020 . 33281831 . 7689341 . 10.3389/fimmu.2020.606489 . free .
  4. Fox LE, Locke MC, Lenschow DJ . Context Is Key: Delineating the Unique Functions of IFNα and IFNβ in Disease . Frontiers in Immunology . 11 . 606874 . 2020-12-21 . 33408718 . 7779635 . 10.3389/fimmu.2020.606874 . free .
  5. Dumoutier L, Lejeune D, Hor S, Fickenscher H, Renauld JC . Cloning of a new type II cytokine receptor activating signal transducer and activator of transcription (STAT)1, STAT2 and STAT3 . The Biochemical Journal . 370 . Pt 2 . 391–6 . March 2003 . 12521379 . 1223207 . 10.1042/BJ20021935 .
  6. Xu W, Presnell SR, Parrish-Novak J, Kindsvogel W, Jaspers S, Chen Z, Dillon SR, Gao Z, Gilbert T, Madden K, Schlutsmeyer S, Yao L, Whitmore TE, Chandrasekher Y, Grant FJ, Maurer M, Jelinek L, Storey H, Brender T, Hammond A, Topouzis S, Clegg CH, Foster DC . 6 . A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist . Proceedings of the National Academy of Sciences of the United States of America . 98 . 17 . 9511–6 . August 2001 . 11481447 . 55483 . 10.1073/pnas.171303198 . 2001PNAS...98.9511X . vanc . free .