IL-13 receptor alpha2 promotes epithelial cell regeneration from radiation-induced small intestinal injury in mice.
OBJECTIVE
The cytokines interleukin (IL)-4 and IL-13 have pleiotropic effects on a variety of cell types and impact both pathologic changes and tissue remodeling. The aim of this study was to clarify the roles of IL-13 receptor alpha2 (IL-13Ralpha2), which is the high-affinity decoy receptor for IL-13, in gastrointestinal tract epithelial cell turnover and repair.


METHODS
We have compared the regenerative process following mucosal damage induced by whole-body 3-Gy X-ray irradiation of wild-type (WT) and IL-4 receptor alpha gene-deficient (IL-4R(-/-)) mice. Then we treated mice with IL-13Ralpha2 human immunoglobulin (Ig) chimeric protein.


RESULTS
Up-regulation of mRNA levels for IL-13 in NK cells in the lamina propria was seen after irradiation of WT mice. Concomitant with vigorous epithelial cell division in the jejunum following irradiation, expression of the IL-13Ralpha2 dramatically increased in myofibroblasts and fibroblasts. In contrast, epithelial cell repair was delayed in IL-4R(-/-) mice, which did not show transient up-regulation of IL-13Ralpha2, although up-regulation of IL-13 was seen. Addition of IL-13 but not IL-4 to primary cultures of small intestine from both WT and IL-4R(-/-) mice induced epithelial cell damage. Treatment of IL-4R(-/-) mice with IL-13Ralpha2-Ig resulted in increased numbers of dividing epithelial cells and improved tissue repair after irradiation. Further, treatment with IL-13Ralpha2-Ig increased numbers of microcolonies of regenerating epithelial cells in the intestine of WT mice after severe damage induced by 12-Gy irradiation.


CONCLUSIONS
The IL-13Ralpha2 is a major regulatory factor involved in the regeneration of epithelial cells in the gastrointestinal tract.
Kawashima
Rei
R
Department of Gastroenterology, Research Institute, International Medical Center of Japan, Tokyo, Japan.
Kawamura
Yuki I
YI
Kato
Rie
R
Mizutani
Noriko
N
Toyama-Sorimachi
Noriko
N
Dohi
Taeko
T
D000818:Animals; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D053661:Interleukin-13 Receptor alpha1 Subunit; D007583:Jejunum / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000473:pathology; D018123:Receptors, Interleukin / Q000627:therapeutic use*; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects*; D015854:Up-Regulation
C508181:IL13RA1 protein, human; C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D007371:Interferon-gamma