Tissue-Resident Regulatory T Cells Expressing CD83 Maintain Local Homeostasis and Restrict Th2 Responses in Asthma

Area of Science:

• Immunology
• Respiratory Medicine
• Cell Biology

Background:

• Non-lymphoid tissue regulatory T cells (NLT-Tregs) maintain tissue health and control inflammation.
• CD83 is identified as a marker for NLT-Tregs, but its specific function in these cells remains unclear.
• Understanding CD83's role is vital for comprehending tissue homeostasis and immune responses in barrier tissues.

Purpose of the Study:

• To investigate the biological significance of CD83 expression in lung-resident Tregs.
• To determine the role of CD83 in steady-state conditions and during asthma pathogenesis.
• To elucidate CD83's impact on T-cell populations and inflammatory responses in the lungs.

Main Methods:

• Generated Treg-specific CD83 knockout (CD83cKO) mice.
• Analyzed lung-resident T-cell populations and cytokine profiles in CD83cKO mice.
• Utilized an asthma model to assess disease progression and T-helper cell responses in CD83cKO mice.

Main Results:

• CD83-deficient lung Tregs showed reduced differentiation but increased activation, leading to uncontrolled T-cell activation.
• CD83cKO mice exhibited accelerated asthma progression, characterized by a Th2-biased immune response.
• CD83cKO Tregs displayed heightened responsiveness to IL-4, impairing the control of naive T-cell differentiation towards Th2 cells.

Conclusions:

• CD83 plays a critical role in regulating Th2 responses mediated by NLT-Tregs.
• The absence of CD83 disrupts lung homeostasis and exacerbates asthma.
• CD83 is a key regulator of inflammatory responses, with potential therapeutic implications for asthma and other inflammatory diseases.