Cloning and characterization of mouse IL-22 binding protein

Abstract

Interleukin-22 (IL-22), a member of IL-10 family, plays some important roles in immune response through activation of the STAT 3 signal transduction pathway. Two types of IL-22-binding receptor have been discovered, a membrane-bound receptor and a soluble receptor, both encoded by different genes. IL-22 may be involved in inflammatory processes specifically regulated by soluble receptors. By screening a mouse genomic library for a human IL-22 binding protein homologue, we identified the mouse genomic clone of IL-22 binding protein. Its coding sequence was verified and isolated by RT-PCR. The gene encodes a protein of 230 amino acids that share 67.1% amino-acid sequence identity with human IL-22 binding protein.We designated this receptor 'mouse IL-22 binding protein' (mIL-22BP). mIL-22BP could be upregulated by LPS stimulation in mouse monocytes. mIL-22BP binds to mouse and human IL-22 and neutralizes STAT3 activation induced by both cytokines in human and rat hepatoma cell lines. Treating B cells with mouse IL-22 induces production of reactive oxygen species, which mIL-22BP blocks.

Cytokines and effector T cell subsets causing autoimmune CNS disease

“…Binding of IL-22 to its receptor activates Jak-Stat signaling pathways, in particular Stat3. In addition to the cell surface receptor complex, there is a secreted IL-22 binding receptor, termed IL-22 binding protein (IL-22BP), which is encoded by an independent gene that lacks sequences for the intracellular and transmembrane domains of IL-22R [107][108][109][110]. In vitro, IL-22BP binds IL-22 and inhibits the binding of IL-22 to its cell membrane associated receptor.…”

The IL-10R2 Binding Hot Spot on IL-22 is Located on the N-terminal Helix and is Dependent on N-linked Glycosylation

“…1,3 IL-22 also induces reactive oxygen species in B cells. 4 IL-22 is a member of the class 2 a-helical cytokine family and shares limited sequence identity with IL-10, 1,2 IL-19, 5 IL-20, 6 IL-24, 7 IL-26, 8 and the interferon-like cytokines IL-28A, IL-28B, and IL-29. [9][10][11] The signaling paradigm for these cytokines requires each molecule to engage at least two membrane-spanning receptors, one each of two subtypes (type I and type II).…”

A novel transcript of mouse interleukin-20 receptor acts on glomerular mesangial cells as an aggravating factor in lupus nephritis

“…[21][22][23][24][25][26] Within the CRF2 family, only IL-22 binding protein was identified as a decoy receptor functioning as a naturally occurring, highly specific IL-22 antagonist in both humans [27][28][29] and mice. 30 Therefore, we aimed to discover any soluble receptors of IL-20R1. We used RT-PCR to detect the transcript variants of membraneform receptor, mIL-20R1, generated by alternative splicing of mRNA transcripts.…”