Tissue-specific pathways extrude activated ILC2s to disseminate type 2 immunity

Area of Science:

• Immunology
• Cell Biology

Background:

• Group 2 innate lymphoid cells (ILC2s) are crucial immune cells residing at barrier tissues.
• While ILC precursors circulate in the blood, mature ILC2s can enter circulation following helminth infection, migrating to distant sites to aid tissue repair.

Purpose of the Study:

• To investigate the origin and heterogeneity of circulating ILC2s.
• To understand how local ILC2 activation leads to systemic immune responses.

Main Methods:

• Utilized fate-mapping techniques in a Nippostrongylus brasiliensis infection model.
• Employed methods to bypass specific infection phases (lung, intestinal) to track ILC2s.
• Analyzed ILC2 populations based on tissue origin and alarmin receptor profiles.

Main Results:

• Blood ILC2s are heterogeneous, originating from distinct tissues.
• Tissue-specific alarmins activate local ILC2s, prompting proliferation and migration.
• Activated ILC2s disseminate into the bloodstream, distributing type 2 cytokines systemically.

Conclusions:

• Local ILC2 activation can initiate systemic type 2 immune responses.
• The extrusion of activated sentinel ILC2s from tissues into circulation is a key mechanism for this transition.