Functional implications for signaling via the IL4R/IL13R complex on bovinecells

IL-4 and IL-13 share a wide range of activities on monocytes, epithelial ce lls and B cells and thus play an important role in host defense. Many of th ese activities are not conserved among species as human, but not murine, B cells are thought to be responsive to IL-13. We previously demonstrated tha t human IL-13 is highly conserved at the nucleic acid level with a candidat e bovine IL-13 cDNA homologue. Moreover, recombinant human IL-13 stimulates Ig secretion by appropriately activated bovine B cells. These studies have been extended to examining Ig class switching at both the protein and mRNA levels in addition to examining other markers of cellular activation. Our results suggest that IL-13 influences B cell differentiation by enhancing I gM, IgG1, and IgE production. IL-13 stimulation alone increases MHC class I I expression and progression through cell cycle, although at lower levels i n comparison to rboIL-4. The biology of the receptors for IL-4 and IL-13 is complex and raises sever al key questions with regard to IL-4-dependent and -independent mechanisms of host immunomodulation. Recent studies suggest that at least four chains are involved. These include the p140 IL-4 binding chain (IL-4R alpha), the common gamma chain (gamma c chain), IL-13 receptor alpha-1 chain (IL-13R al pha-1) and the IL-13 receptor alpha 2 chain (IL-13R alpha-2). We have recen tly cloned cDNAs for the bovine homologues of the IL-13R alpha-1 and IL-4R alpha chains and evaluated mRNA expression for a variety of cell types foll owing stimulation. The expression patterns and their implications for recep tor chain utilization in signaling via these key TH2 signature cytokines wi ll be discussed. (C) 1999 Elsevier Science B.V. All rights reserved.