Trefoil factor 2 (TFF2) deficiency in murine digestive tract influences the immune system.
OBJECTIVE
The gastrointestinal trefoil factor family (TFF1, TFF2, TFF3) peptides are considered to play an important role in maintaining the integrity of the mucosa. The physiological role of TFF2 in the protection of the GI tract was investigated in TFF2 deficiency.


METHODS
TFF2-/- mice were generated and differential expression of various genes was assessed by using a mouse expression microarray, quantitative real time PCR, Northern blots or immunohistochemistry.


RESULTS
On an mRNA level we found 128 differentially expressed genes. We observed modulation of a number of crucial genes involved in innate and adaptive immunity in the TFF2-/- mice. Expression of proteasomal subunits genes (LMP2, LMP7 and PSMB5) involved in the MHC class I presentation pathway were modulated indicating the formation of immunoproteasomes improving antigen presentation. Expression of one subunit of a transporter (TAP1) responsible for importing degraded antigens into ER was increased, similarly to the BAG2 gene that modulates chaperone activity in ER helping proper loading on MHC class I molecules. Several mouse defensin (cryptdin) genes coding important intestinal microbicidal proteins were up-regulated as a consequence of TFF2 deficiency. Normally moderate expression of TFF3 was highly increased in stomach.
Baus-Loncar
Mirela
M
Division of Molecular Genetics, Institute of Human Genetics, University of Tuebingen, Germany.
Schmid
Janinne
J
Lalani
El-Nasir
el-N
Rosewell
Ian
I
Goodlad
Robert A
RA
Stamp
Gordon W H
GW
Blin
Nikolaus
N
Kayademir
Tuncay
T
D000818:Animals; D017951:Antigen Presentation; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004064:Digestive System / Q000276:immunology* / Q000378:metabolism*; D020869:Gene Expression Profiling; D018390:Gene Targeting; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009077:Mucins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D000071164:Trefoil Factor-2
D017931:DNA Primers; D015395:Histocompatibility Antigens Class I; D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; D011498:Protein Precursors; C000604007:TFF2 protein, human; C481546:TFF2 protein, mouse; D000071164:Trefoil Factor-2; C059569:cryptdin; D046988:Proteasome Endopeptidase Complex