Potential role of thioredoxin in immune responses in intestinal lamina propria T lymphocytes.
Thioredoxin (TRX) is a ubiquitous oxidoreductase with strong co-cytokine, chemoattractant and anti-apoptotic activities. TRX expression was found to be particularly elevated in the intestinal mucosa, where its physiologic function is entirely unknown. Here, we demonstrate a high level of TRX expression in lamina propria T cells (LP-T) as opposed to autologous peripheral blood T lymphocytes (PB-T). Addition of recombinant human TRX (rhTRX) to PB-T enhances TRX gene expression. This autoregulation involves the calcineurin signaling pathway, as rhTRX antagonizes the cyclosporine A (CsA)- and tacrolimus-mediated suppression of TRX gene expression. Similarly, rhTRX reverses the suppression of IL-2 mRNA production by CsA and enhances cytokine production preferentially in prestimulated cells. The differential TRX expression in LP-T versus PB-T may thus contribute to the high-level, CsA-resistant IL-2 production characteristic for CD2-stimulated LP-T. Inversely, inactivation of TRX in LP-T through inhibition of TRX reductase abolishes cytokine gene expression. TRX may play a key role in the specialized intestinal microenvironment in amplifying immediate immune responses of LP-T whenever appropriate costimulation of LP-T is provided.
Sido
Bernd
B
Department of Surgery, University of Heidelberg, Heidelberg, Germany.
Giese
Thomas
T
Autschbach
Frank
F
Lasitschka
Felix
F
Braunstein
Jutta
J
Meuer
Stefan C
SC
D003001:Cloning, Molecular; D003106:Colon / Q000166:cytology / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors; D013879:Thioredoxins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D007376:Interleukin-2; D012333:RNA, Messenger; D013879:Thioredoxins; D013880:Thioredoxin-Disulfide Reductase