| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Institut für Klinische Mikrobiologie, Immunologie, und Hygiene der Universität Erlangen-Nürnberg, Erlangen, Germany
IL-4 is a pleiotropic cytokine that is essential for the
differentiation of Th2 cells and is critically involved in the
pathogenesis of certain infectious and allergic diseases. We have
produced and functionally characterized a mutant of murine IL-4
(IL-4.Y119D) as a potential antagonist of IL-4. The analysis of IL-4R
binding revealed no differences between wild-type and mutated IL-4.
Despite this finding, IL-4.Y119D was unable to induce proliferation of
several IL-4-responsive T cell lines mediated via the type I IL-4R
(IL-4R
/common 
chain (c chain)) and specifically inhibited the
proliferative effect of wild-type IL-4. In contrast, with IL-4.Y119D we
found induction of MHC class II and CD23 molecules on resting splenic B
cells as well as proliferation of B9 plasmocytoma cells. In addition,
IL-4.Y119D induced mRNA for soluble IL-4R, leading to the release of
soluble IL-4R protein by spleen cells. In macrophages, mutated IL-4 in
combination with IFN- induced TNF--dependent killing of
Leishmania major parasites such as wild-type IL-4. The
agonistic effects of IL-4.Y119D were observed on cells expressing the
IL-13R -chain, including an IL-13R -chain transfected T cell
line, but were absent in T cells that lack this molecule, indicating
that IL-4.Y119D conveys its activity via the type II IL-4R
(IL-4R/IL-13R). The described IL-4 mutant, therefore, represents
a new tool to use in dissecting different IL-4 functions that are
mediated by either type I or type II IL-4R
complexes.
This article has been cited by other articles:
|
|
 |
|
  H.-H. Lee, C. M. Hoeman, J. C. Hardaway, F. B. Guloglu, J. S. Ellis, R. Jain, R. Divekar, D. M. Tartar, C. L. Haymaker, and H. Zaghouani Delayed maturation of an IL-12-producing dendritic cell subset explains the early Th2 bias in neonatal immunity J. Exp. Med., September 29, 2008; 205(10): 2269 - 2280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Yao, W. Chen, H. Luo, Q. Jiang, Z. Xia, L. Zang, J. Zuo, X. Wei, Z. Chen, X. Shen, et al. Identification of core functional region of murine IL-4 using peptide phage display and molecular modeling Int. Immunol., January 1, 2006; 18(1): 19 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Rafalska, Z. Zhang, N. Benderska, H. Wolff, A. M. Hartmann, R. Brack-Werner, and S. Stamm The intranuclear localization and function of YT521-B is regulated by tyrosine phosphorylation Hum. Mol. Genet., August 1, 2004; 13(15): 1535 - 1549. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Lutz, M. Schnare, M. Menges, S. Rossner, M. Rollinghoff, G. Schuler, and A. Gessner Differential Functions of IL-4 Receptor Types I and II for Dendritic Cell Maturation and IL-12 Production and Their Dependency on GM-CSF J. Immunol., October 1, 2002; 169(7): 3574 - 3580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tomkinson, C. Duez, G. Cieslewicz, J. C. Pratt, A. Joetham, M.-C. Shanafelt, R. Gundel, and E. W. Gelfand A Murine IL-4 Receptor Antagonist That Inhibits IL-4- and IL-13-Induced Responses Prevents Antigen-Induced Airway Eosinophilia and Airway Hyperresponsiveness J. Immunol., May 1, 2001; 166(9): 5792 - 5800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Suzuki, H. Nakajima, N. Watanabe, S.-i. Kagami, A. Suto, Y. Saito, T. Saito, and I. Iwamoto Role of common cytokine receptor gamma chain (gamma c)- and Jak3-dependent signaling in the proliferation and survival of murine mast cells Blood, September 15, 2000; 96(6): 2172 - 2180. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
