title: Temporal associations between interleukin 22 and the extracellular domains of IL-22R and IL-10R2.
abstract: Interleukin 22 (IL-22) is a cytokine induced during both innate and adaptive immune responses. It can effect an acute phase response, implicating a role for IL-22 in mechanisms of inflammation. IL-22 requires the presence of the IL-22 receptor (IL-22R) and IL-10 receptor 2 (IL-10R2) chains, two members of the class II cytokine receptor family (CRF2), to effect signal transduction within a cell. We studied the interaction between human IL-22 and the extracellular domains (ECD) of its receptor chains in an enzyme-linked immunoabsorbant assay (ELISA)-based format, using biotinylated IL-22 (bio-IL-22) and receptor-fusions containing the ECD of a receptor fused to the Fc of hIgG1 (IL-22R-Fc and IL-10R2-Fc). IL-22 has measurable affinity for IL-22R-Fc homodimer and undetectable affinity for IL-10R2. IL-22 has substantially greater affinity for IL-22R/IL-10R2-Fc heterodimers. Further analyses involving sequential additions of receptor homodimers and cytokine indicates that the IL-10R2(ECD) binds to a surface created by the interaction between IL-22 and the IL-22R(ECD), and thereby further stabilizes the association of IL-22 within this cytokine-receptor-Fc complex. Both a neutralizing rat monoclonal antibody, specific for human IL-22, and human IL-22BP-Fc, an Fc-fusion of the secreted IL-22 binding-protein and proposed natural antagonist for IL-22, bind to similar cytokine epitopes that may overlap the binding site for IL-22R(ECD). Another rat monoclonal antibody, specific for IL-22, binds to an epitope that may overlap a separate binding site for IL-10R2(ECD). We propose, based on this data, a temporal model for the development of a functional IL-22 cytokine-receptor complex.
authors.affiliation: Wyeth Research, 87 Cambridge Park Drive, Cambridge, MA 02140, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Kathy N
authors.initials: KN
authors.lastname: Tomkinson
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Tan
authors.forename: Paul
authors.initials: P
authors.lastname: Wu
authors.forename: Grace
authors.initials: G
authors.lastname: Yan
authors.forename: Vikki
authors.initials: V
authors.lastname: Spaulding
authors.forename: Bijia
authors.initials: B
authors.lastname: Deng
authors.forename: Bethany
authors.initials: B
authors.lastname: Annis-Freeman
authors.forename: Kathleen
authors.initials: K
authors.lastname: Heveron
authors.forename: Richard
authors.initials: R
authors.lastname: Zollner
authors.forename: Gerard
authors.initials: G
authors.lastname: De Zutter
authors.forename: Jill F
authors.initials: JF
authors.lastname: Wright
authors.forename: Tara K
authors.initials: TK
authors.lastname: Crawford
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jacobs
authors.forename: Neil M
authors.initials: NM
authors.lastname: Wolfman
authors.forename: Vincent
authors.initials: V
authors.lastname: Ling
authors.forename: Debra D
authors.initials: DD
authors.lastname: Pittman
authors.forename: Geertruida M
authors.initials: GM
authors.lastname: Veldman
authors.forename: Lynette A
authors.initials: LA
authors.lastname: Fouser
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D019281:Dimerization; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology; D018123:Receptors, Interleukin / Q000187:drug effects / Q000378:metabolism*; D053701:Receptors, Interleukin-10; D013997:Time Factors; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D000097043:Interleukin-22; C415369:interleukin-22 receptor