Expression and regulation of IL-22 by bovine peripheral blood gamma/delta T cells.
IL-22 is a novel T and NK cell cytokine that belongs to the IL-10 cytokine family. Here we report the identification of a bovine IL-22 ortholog that is expressed by mitogen activated bovine peripheral blood gamma/delta T cells. The full-length bovine IL-22 cDNA contained a 68 bp 5'-untranslated region (UTR), a 570-bp open reading frame, and a 480-bp 3'-UTR. The deduced pre-IL-22 has 190 amino acid residues containing a secretory signal peptide from amino acids 1-33 and several potential N-glycosylation sites. The mature protein is predicted to be a secreted, alpha-helical molecule. The bovine IL-22 gene is approximately 7.5 kb in length and is comprised of five introns and six exons, and the first exon is non-coding. Computer analysis and gel shift assay showed that the -1132 and -879 region in the 5' upstream gene sequence contained putative transcription factor binding sites for STATx, Sox-5/9, Sp1, Ik-1, and AREB6. Mutagenesis of STATx and Sox5/9 binding sites decreased promoter functionality by approximately 50%, suggesting their importance in transcription regulation of IL-22. Expression of IL-22 transcripts induced by various mitogens indicated existence of two regulatory control pathways in gamma/delta T cells; IL-2 or PMA treatment induced a slow accumulation of IL-22 mRNA without affecting the maximum induction pathway, whereas ConA treatment rapidly induced a limited amount of IL-22 transcripts. Similar maximal levels of IL-22 transcripts could be induced in gamma/delta T cells and alpha/beta T cells. We conclude that bovine gamma/delta T cells are important sources of IL-22 and suggest a role for this cytokine in regulating immune responses at mucosal surfaces, including the gut.
Ma
Shi-Dong
SD
Department of Veterinary and Biomedical Sciences, University of Minnesota, 1988 Fitch Avenue, Room 295 AS/VM, St. Paul, MN 55108, USA.
Lancto
Cheryl A
CA
Enomoto
Shinichiro
S
Abrahamsen
Mitchell S
MS
Rutherford
Mark S
MS
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle / Q000276:immunology* / Q000378:metabolism*; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D018928:Immunity, Mucosal; D007378:Interleukins / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D000097043:Interleukin-22
D007378:Interleukins; D000097043:Interleukin-22