| Structural highlights
Function
IL21_HUMAN Cytokine with immunoregulatory activity. May promote the transition between innate and adaptive immunity. Induces the production of IgG(1) and IgG(3) in B-cells (By similarity). May play a role in proliferation and maturation of natural killer (NK) cells in synergy with IL15. May regulate proliferation of mature B- and T-cells in response to activating stimuli. In synergy with IL15 and IL18 stimulates interferon gamma production in T-cells and NK cells. During T-cell mediated immune response may inhibit dendritic cells (DC) activation and maturation.[1] [2]
Publication Abstract from PubMed
Interleukin-21 (IL-21) plays a critical role in generating immunological memory by promoting the germinal center reaction, yet clinical use of IL-21 remains challenging because of its pleiotropy and association with autoimmune disease. To better understand the structural basis of IL-21 signaling, we determine the structure of the IL-21-IL-21R-gammac ternary signaling complex by X-ray crystallography and a structure of a dimer of trimeric complexes using cryo-electron microscopy. Guided by the structure, we design analogs of IL-21 by introducing substitutions to the IL-21-gammac interface. These IL-21 analogs act as partial agonists that modulate downstream activation of pS6, pSTAT3, and pSTAT1. These analogs exhibit differential activity on T and B cell subsets and modulate antibody production in human tonsil organoids. These results clarify the structural basis of IL-21 signaling and offer a potential strategy for tunable manipulation of humoral immunity.
A structural blueprint for interleukin-21 signal modulation.,Abhiraman GC, Bruun TUJ, Caveney NA, Su LL, Saxton RA, Yin Q, Tang S, Davis MM, Jude KM, Garcia KC Cell Rep. 2023 Jun 19;42(6):112657. doi: 10.1016/j.celrep.2023.112657. PMID:37339051[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, Johnston J, Madden K, Xu W, West J, Schrader S, Burkhead S, Heipel M, Brandt C, Kuijper JL, Kramer J, Conklin D, Presnell SR, Berry J, Shiota F, Bort S, Hambly K, Mudri S, Clegg C, Moore M, Grant FJ, Lofton-Day C, Gilbert T, Rayond F, Ching A, Yao L, Smith D, Webster P, Whitmore T, Maurer M, Kaushansky K, Holly RD, Foster D. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature. 2000 Nov 2;408(6808):57-63. PMID:11081504 doi:http://dx.doi.org/10.1038/35040504
- ↑ Strengell M, Julkunen I, Matikainen S. IFN-alpha regulates IL-21 and IL-21R expression in human NK and T cells. J Leukoc Biol. 2004 Aug;76(2):416-22. Epub 2004 Jun 3. PMID:15178704 doi:http://dx.doi.org/10.1189/jlb.1003488
- ↑ Abhiraman GC, Bruun TUJ, Caveney NA, Su LL, Saxton RA, Yin Q, Tang S, Davis MM, Jude KM, Garcia KC. A structural blueprint for interleukin-21 signal modulation. Cell Rep. 2023 Jun 19;42(6):112657. PMID:37339051 doi:10.1016/j.celrep.2023.112657
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