Functional importance of regional differences in localized gene expression of receptors for IL-13 in murine gut.
IL-13 induces a STAT6-dependent hypercontractility of intestinal smooth muscle that is mediated by binding to the IL-13Ralpha1 component of the type 2 IL-4R that is linked to STAT6. IL-13 also binds to the IL-13Ralpha2 that is not linked to STAT6 and functions to limit the effects of IL-13 in vivo. In this study we assessed the contributions of regional and cellular differences in the distribution of the IL-13R components to the physiological regulation of smooth muscle function in wild-type mice and mice deficient in STAT6 or IL-13Ralpha2. The expression of IL-13 and IL-13Ralpha2 was higher in colon than in small intestine. Laser capture microdissection of specific cell types revealed that the expression of IL-13Ralpha2 was higher in the smooth muscle layer compared with levels in the epithelial cells of the mucosa. In contrast, there was a uniform distribution of IL-13alpha1 in smooth muscle, epithelia, and myenteric neurons. The significant hypercontractility of smooth muscle in mice deficient in IL-13Ralpha2, but not in STAT6, shows the physiological importance of IL-13 binding to IL-13Ralpha2. The pronounced differences in the expression of IL-13Ralpha2 suggest that the gut has developed sophisticated mechanisms for controlling the physiological and pathophysiological activities of IL-13.
Morimoto
Motoko
M
Department of Medicine and Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Morimoto
Masahiro
M
Zhao
Aiping
A
Madden
Kathleen B
KB
Dawson
Harry
H
Finkelman
Fred D
FD
Mentink-Kane
Margaret
M
Urban
Joseph F
JF
Wynn
Thomas A
TA
Shea-Donohue
Terez
T
D000818:Animals; D005769:Gastrointestinal Motility / Q000276:immunology; D015870:Gene Expression; D053661:Interleukin-13 Receptor alpha1 Subunit; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D007834:Lasers; D051379:Mice; D008807:Mice, Inbred BALB C; D042282:Microdissection; D009119:Muscle Contraction / Q000276:immunology; D009130:Muscle, Smooth / Q000276:immunology / Q000378:metabolism; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics*; D053660:Receptors, Interleukin-13; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050800:STAT6 Transcription Factor / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics
C508183:Il13ra1 protein, mouse; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse