Group 2 Innate Lymphoid Cells Attenuate Inflammatory Arthritis and Protect from Bone Destruction in Mice

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation.
• Group 2 innate lymphoid cells (ILC2s) are immune cells implicated in various inflammatory conditions.

Purpose of the Study:

• To investigate the role of ILC2s in the pathogenesis of rheumatoid arthritis.
• To determine whether ILC2s possess immune-regulatory functions in arthritis models.

Main Methods:

• Flow cytometry was used to detect and quantify ILC2s in patients with RA and in mouse models of arthritis (SIA and CIA).
• Loss-of-function (RORαcre/GATA3fl/fl, Tie2cre/RORαfl/fl mice) and gain-of-function (IL-25/IL-33, IL-2/IL-2 antibody complex, adoptive transfer) mouse models were employed.
• Adoptive transfer experiments using wild-type (WT) and IL-4/13 knockout ILC2s were performed.

Main Results:

• Circulating ILC2s were significantly increased in RA patients and inversely correlated with disease activity.
• Arthritis induction in mice rapidly increased ILC2 numbers.
• Reducing ILC2s exacerbated arthritis, whereas increasing ILC2s or transferring WT ILC2s attenuated arthritis, particularly during the initiation phase.
• Transfer of IL-4/13-competent ILC2s, but not IL-4/13-deficient ILC2s, reduced macrophage cytokine secretion.

Conclusions:

• ILC2s are present in RA and play a significant immune-regulatory role in arthritis.
• ILC2s modulate arthritis severity, suggesting therapeutic potential.
• The anti-arthritic effects of ILC2s involve the regulation of macrophage cytokine production via IL-4 and IL-13.