Genome-wide expression profiling during protection from colitis by regulatory T cells.
BACKGROUND
In the adoptive transfer model of colitis it has been shown that regulatory T cells (Treg) can hinder disease development and cure already existing mild colitis. The mechanisms underlying this regulatory effect of CD4(+)CD25(+) Tregs are not well understood.


METHODS
To identify pathways of importance for immune regulation in protected mice we studied the genome-wide expression profile in the inflamed rectum of SCID mice with CD4(+) T cell transfer colitis and in the uninflamed rectum of mice protected from colitis by Treg cells. We used DNA microarray technology (Affymetrix GeneChip Mouse Genome 430 2.0 Array), which enabled an analysis of a complete set of RNA transcript levels in each sample. Array results were confirmed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR).


RESULTS
Data were analyzed using combined projections to latent structures and functional annotation analysis. The colitic samples were clearly distinguishable from samples from normal mice by a vast number of inflammation- and growth factor-related transcripts. In contrast, the Treg-protected animals could not be distinguished from either the normal BALB/c mice or the normal SCID mice. mRNA expression profiles of cytokine, chemokine, and growth factor genes were significantly altered in colitic as opposed to noncolitic mice. In particular, the transcription factors STAT3, GATA2, and NFkappaB, the cytokine IL1beta, and the chemokine receptors CXCR3 and CCR1 as well as their ligands all seemingly play central roles in the inflammatory processes.


CONCLUSIONS
We suggest that these molecules alone or in combination could be future therapeutic targets.
Kristensen
Nanna Ny
NN
Department of International Health, Immunology and Microbiology, University of Copenhagen, Panum Institute, Denmark. n.n.kristensen@mai.ku.dk
Olsen
Jørgen
J
Gad
Monika
M
Claesson
Mogens Helweg
MH
D000818:Animals; D003092:Colitis / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics; D012007:Rectum / Q000276:immunology / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D019707:Receptors, Chemokine; D014157:Transcription Factors