Intestinal intraepithelial lymphocytes prevent pathogen-driven inflammation and regulate the Smad/T-bet pathway of lamina propria CD4+ T cells.
Intraepithelial lymphocytes (IEL) play a key role in gut homeostasis and are critical effector cells preventing the inflammatory intestinal lesions induced in mice following oral infection with Toxoplasma gondii. In this intestinal inflammatory model, CD4(+) T lymphocytes from the lamina propria (LP) synergize with the infected enterocytes to secrete pro-inflammatory chemokines and cytokines. In this study, we assessed the mechanisms accounting for the ability of IEL to modulate the inflammatory activity of these cells. Adoptive transfer of IEL purified from wild-type mice, or CD154-,CD95L- or IL-10-deficient mice infected with T. gondii completely impairs the development of the lethal ileitis in recipient mice orally infected with T. gondii. Compared with unprimed IEL isolated from naive mice, the CD8 alpha beta TCR alpha beta subset of primed IEL, isolated from T. gondii-infected mice, secretes increased amount of TGF-beta. IEL interact with the LP CD4(+) T lymphocytes, down-regulate their production of inflammatory cytokines such as IFN-gamma and reduce their proliferative activity. These effects are linked to the secretion of TGF-beta and are correlated with a shift in the balance between Smad7/T-bet down-regulation and Smad2/Smad3 up-regulation in LP CD4(+) T lymphocytes.
Mennechet
Franck J D
FJ
Department of Microbiology, Dartmouth Medical School, Lebanon, NH, USA.
Kasper
Lloyd H
LH
Rachinel
Nicolas
N
Minns
Laurie A
LA
Luangsay
Souphalone
S
Vandewalle
Alain
A
Buzoni-Gatel
Dominique
D
D019264:Adoptive Transfer; D000818:Animals; D004268:DNA-Binding Proteins / Q000276:immunology*; D005260:Female; D007079:Ileitis / Q000276:immunology* / Q000469:parasitology; D015151:Immunoblotting; D007249:Inflammation / Q000276:immunology* / Q000469:parasitology; D007413:Intestinal Mucosa / Q000276:immunology / Q000469:parasitology; D007422:Intestines / Q000276:immunology / Q000469:parasitology; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D051785:Smad Proteins; D013601:T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D014122:Toxoplasma / Q000276:immunology; D014123:Toxoplasmosis / Q000276:immunology; D015534:Trans-Activators / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology
D004268:DNA-Binding Proteins; D051785:Smad Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta