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An IL-27/Lag3 axis enhances Foxp3+ regulatory T cell-suppressive function and therapeutic efficacy
J-S Do1, A Visperas1,2, Y O Sanogo3
1Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Mucosal Immunology
|May 28, 2015
Summary
Interleukin-27 (IL-27) enhances regulatory T cell (Treg) function, improving immune tolerance. This cytokine boosts Treg
Area of Science:
- Immunology
- Cellular Biology
- Inflammation Research
Background:
- Foxp3-expressing regulatory T cells (Tregs) are crucial for immune homeostasis and preventing autoimmunity.
- Treg function can be impaired during inflammatory conditions, necessitating strategies to enhance their activity.
- Interleukin-27 (IL-27), a cytokine with complex roles in T cell responses, is investigated for its impact on Treg function.
Purpose of the Study:
- To investigate the role of IL-27 in modulating the function of regulatory T cells (Tregs).
- To determine if IL-27 can enhance Treg suppressive capabilities, particularly in the context of inflammatory bowel disease (IBD).
- To identify potential molecular mechanisms, such as the expression of specific surface molecules, through which IL-27 exerts its effects on Tregs.
Main Methods:
- Utilized a mouse model of T cell-induced colitis, a model relevant to human inflammatory bowel disease (IBD).
- Compared the function of wild-type (WT) Tregs with IL-27 receptor-deficient (IL-27R-deficient) Tregs in vitro and in vivo.
- Assessed Treg suppressive capacity, inflammatory cytokine production, and the expression of surface molecules like Lag3 following IL-27 stimulation.
- Examined the effect of IL-27 stimulation on human Tregs.
Main Results:
- IL-27 significantly enhanced the suppressive function of Tregs, both in vitro and in vivo.
- IL-27R-deficient Tregs showed impaired ability to control T cell-induced colitis compared to WT Tregs.
- IL-27 stimulation induced the expression of Lag3 on Tregs, which was found to be critical for their suppressive function.
- Human Tregs also exhibited enhanced suppressive function and increased Lag3 expression upon IL-27 stimulation.
Conclusions:
- IL-27 plays a key role in enhancing Treg function to control intestinal inflammation, as demonstrated in a colitis model.
- The IL-27-induced expression of Lag3 on Tregs is essential for mediating their suppressive activity against inflammatory responses.
- The IL-27/Lag3 axis represents a novel pathway for modulating Treg function and offers potential therapeutic targets for inflammatory conditions like IBD.
