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

RR Ricardo-Gonzalez, C Schneider, C Liao… - Journal of Experimental …, 2020 - rupress.org
RR Ricardo-Gonzalez, C Schneider, C Liao, J Lee, HE Liang, RM Locksley
Journal of Experimental Medicine, 2020rupress.org
Group 2 innate lymphoid cells (ILC2s) are tissue-resident cells prominent at barrier sites.
Although precursors are found in blood, mature ILC2s can enter the circulation after small
intestinal perturbation by migratory helminths and move to distant tissues to influence the
local reparative response. Using fate-mapping and methods to bypass the lung or intestinal
phases of Nippostrongylus brasiliensis infection, we show that blood ILC2s comprise
heterogeneous populations derived from distinct tissues that are dependent on alarmins …
Group 2 innate lymphoid cells (ILC2s) are tissue-resident cells prominent at barrier sites. Although precursors are found in blood, mature ILC2s can enter the circulation after small intestinal perturbation by migratory helminths and move to distant tissues to influence the local reparative response. Using fate-mapping and methods to bypass the lung or intestinal phases of Nippostrongylus brasiliensis infection, we show that blood ILC2s comprise heterogeneous populations derived from distinct tissues that are dependent on alarmins matched to the receptor profile of the specific tissue ILC2s. Activation of local ILC2s by tissue-specific alarmins induced their proliferation, lymph node migration, and blood dissemination, thus systemically distributing type 2 cytokines. These studies uncover a possible mechanism by which local innate responses transition to systemic type 2 responses by extrusion of activated sentinel ILC2s from tissue into the circulation.
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