IL-6 effector function of group 2 innate lymphoid cells (ILC2) is NOD2 dependent

Area of Science:

• Immunology
• Dermatology
• Cell Biology

Background:

• Group 2 innate lymphoid cells (ILC2) are crucial for skin immunity, responding to barrier damage.
• ILC2 typically activate via cytokines, lacking antigen-specific receptors.
• Their direct sensing of pathogens remains incompletely understood.

Purpose of the Study:

• To investigate the direct sensing capabilities of human cutaneous ILC2 towards skin pathogens and allergens.
• To explore the role of nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and Toll-like receptor 2 (TLR2) in ILC2 activation.

Main Methods:

• RNA sequencing of ILC2 from human skin and blood.
• Stimulation of ILC2 with TLR2 agonists and Staphylococcus aureus muramyl dipeptide (MDP).
• Analysis of ILC2 from patients with NOD2 mutations and assessment of autophagy induction.

Main Results:

• Skin and blood ILC2 express NOD2 and TLR2.
• TLR2 stimulation induced IL-5, IL-13, and IL-6 (with MDP).
• NOD2 signaling regulates IL-6 production and autophagy in ILC2, impaired in NOD2-mutated patients.

Conclusions:

• ILC2 possess a previously unrecognized pathway for direct bacterial sensing via NOD2.
• NOD2 signaling plays a role in differential regulation of ILC2-derived IL-6 and autophagy.
• This finding expands our understanding of ILC2's role in skin immunity and host defense.