The signaling function of the IL-13Ralpha2 receptor in the development of gastrointestinal fibrosis and cancer surveillance.
The IL-13Ralpha2 receptor is a high affinity receptor for IL-13 that is used only by IL-13 and is quite distinct from the well known IL-13Ralpha1 receptor that IL-13 shares with IL-4. It was widely considered to be a secreted receptor that is devoid of signaling activity and functional only as a decoy receptor that retarded signaling via IL-13Ralpha1. In recent studies, however, it was shown to be capable of robust signaling that results in production of TGF-beta1 and through the latter cytokine, the induction of fibrosis occuring in various experimental inflammatory states. Thus, in initial studies, IL-13 signaling via IL-13Ralpha2 was shown to play an important role in the fibrosis developing in both oxazolone colitis and bleomycin-induced pulmonary fibrosis; later, it was also shown to be critical to the development of fibrosis in a model of chronic colitis induced by trinitrobenzene sulphonic acid (TNBS). These studies suggest that blockade of IL-13 or IL-13Ralpha2 signaling might be an excellent target for the prevention of inflammation-associated fibrosis. A second role of IL-13 signaling via IL-13Ralpha2 is in tumor immune surveillance. Thus, in the relevant studies it was shown that NKT cells stimulated by tumor antigens produce IL-13 that then acts on Gr-1 cells to induce TGF-beta1; the latter then inhibits CD8+ T cells engaged in tumor immune surveillance; in effect, then, receptor signaling favors tumor growth. In addition to its signaling function and the induction of TGF-beta1, IL-13Ralpha2 also influences IL-13Ralpha1 signaling in complex ways; thus, IL-13Ralpha2 emerges as a important component of IL-13 signaling, not only in its own right but also in its possible effect on its companion receptor.
Strober
Warren
W
Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kitani
Atsushi
A
Fichtner-Feigl
Stefan
S
Fuss
Ivan J
IJ
D000818:Animals; D005355:Fibrosis; D041981:Gastrointestinal Tract / Q000473:pathology*; D006801:Humans; D007157:Immunologic Surveillance / Q000276:immunology*; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
D053663:Interleukin-13 Receptor alpha2 Subunit
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