The WSX-1 pathway restrains intestinal T-cell immunity

Area of Science:

• Immunology
• Gastroenterology
• Microbiology

Background:

• Intestinal T-cell accumulation is crucial for managing gut inflammation and has therapeutic potential.
• Interleukin-12 (IL-12) family cytokines play a role in regulating T-cell differentiation during inflammatory responses.

Purpose of the Study:

• To investigate the role of IL-27 in regulating intestinal T-cell accumulation, specifically T helper 17 (T(h)17) cells, during inflammation.
• To explore the potential of targeting IL-27 for therapeutic interventions, particularly in mucosal vaccination.

Main Methods:

• Utilized mouse models deficient in IL-12 (p35(-/-)) and IL-12/IL-23 (p40(-/-)) to assess T(h)17 differentiation.
• Administered lipopolysaccharide (LPS) to induce inflammation and analyzed cytokine levels, including IL-27p28.
• Examined the impact of WSX-1 (IL-27 receptor alpha) deficiency on T-cell populations (T(h)1, T(h)17, regulatory T cells) and their cytokine production (IL-17, IL-10).
• Assessed the expression of α4β7 integrin on T cells from WSX-1 deficient mice.

Main Results:

• LPS induced Staphylococcus aureus enterotoxin A-specific T cells via IL-12 family members.
• IL-12 deficiency favored T(h)17 differentiation, while combined IL-12/IL-23 deficiency reduced T(h)17 cells.
• WSX-1 deficiency led to significant increases in lamina propria T(h)17 cells without affecting T(h)1 cells.
• WSX-1 deficiency increased α4β7 expression on T cells and altered regulatory T cell function, promoting IL-17 and reducing IL-10 production.

Conclusions:

• IL-27 signaling, through WSX-1, restrains T(h)17 cell accumulation in the gut lamina propria.
• Targeting IL-27 may be a viable strategy to enhance T(h)17 cell responses, potentially improving the efficacy of mucosal vaccines.