CD83⁺ B cells alleviate uveitis through inhibiting DCs by sCD83

Area of Science:

• Immunology
• Autoimmune Diseases
• Ophthalmology

Background:

• Soluble CD83 (sCD83) has known immunosuppressive roles in autoimmune diseases like experimental autoimmune uveitis (EAU).
• The specific cell types and molecular mechanisms underlying sCD83's function in EAU remain largely undefined.

Purpose of the Study:

• To identify the cellular source of sCD83 in EAU.
• To elucidate the mechanisms by which sCD83 regulates immune responses in EAU.
• To evaluate the therapeutic potential of CD83-positive B cells in EAU.

Main Methods:

• Identification of CD83-expressing cells in EAU models.
• Analysis of immune cell populations in ocular and lymphoid tissues.
• Assessment of cytokine secretion (IL-1β, IL-18, IFN-γ) from dendritic cells (DCs).
• Investigation of molecular interactions between sCD83, Rab1a, mTORC1, and NLRP3 in DCs.

Main Results:

• CD83-positive B cells were identified as the primary producers of sCD83 in EAU.
• sCD83 secreted by these B cells alleviated EAU symptoms.
• CD83-positive B cells reduced the infiltration of T cells and DCs in affected tissues.
• sCD83 suppressed IL-1β, IL-18, and IFN-γ production by DCs.
• sCD83 promoted Rab1a accumulation in autolysosomes and inhibited mTORC1 phosphorylation and NLRP3 expression in DCs.

Conclusions:

• CD83-positive B cells play a crucial regulatory role in EAU through sCD83 secretion.
• Dysregulation of CD83-positive B cells may contribute to the hyperimmune activation seen in autoimmune uveitis.
• CD83-positive B cells demonstrate potential as a therapeutic strategy for autoimmune uveitis by suppressing activated DCs.