Regulation of mucosal immune responses by recombinant interleukin 10 produced by intestinal epithelial cells in mice.
OBJECTIVE
Interleukin (IL)-10 is a cytokine with anti-inflammatory properties. The aim of this study was to explore the effect of a site-specific delivery of IL-10 on intestinal immune responses.


METHODS
Transgenic mice were created in which IL-10 is expressed by the intestinal epithelial cells.


RESULTS
Transgenic mice showed a marked increase in the number of intraepithelial lymphocytes in the small intestine. Mucosal lymphocytes of transgenic animals produced fewer T helper type 1 cytokines than wild-type lymphocytes. By contrast, the production of transforming growth factor beta was increased. Moreover, the epithelial layer in transgenic mice was significantly enriched for CD4(+)CD25(+) T cells. Furthermore, transgenic mice had increased numbers of immunoglobulin A-producing B cells in the small intestine. These effects were local because splenic lymphocytes were not affected. Studies in models of inflammatory bowel disease showed that transgenic IL-10 was able to attenuate the acute colitis induced by dextran sodium sulfate administration or by adoptive transfer of CD4(+)CD45RB(high) splenocytes, with a modest effect on the chronic intestinal inflammation arising spontaneously in IL-10(-/-) mice.


CONCLUSIONS
These observations provide evidence for an in vivo lymphoepithelial cross talk, by which cytokines locally produced by epithelial cells can regulate immune responses in the intestine without systemic modifications.
De Winter
Hilde
H
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Elewaut
Dirk
D
Turovskaya
Olga
O
Huflejt
Margaret
M
Shimeld
Carolyn
C
Hagenbaugh
Amy
A
Binder
Scott
S
Takahashi
Ichiro
I
Kronenberg
Mitchell
M
Cheroutre
Hilde
H
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D003092:Colitis / Q000517:prevention & control; D016207:Cytokines / Q000096:biosynthesis; D018390:Gene Targeting; D007070:Immunoglobulin A / Q000096:biosynthesis; D016753:Interleukin-10 / Q000235:genetics / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout / Q000235:genetics; D008822:Mice, Transgenic / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D016207:Cytokines; D007070:Immunoglobulin A; D011994:Recombinant Proteins; C508961:Tgfb1 protein, mouse; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10