Migration of Lung Resident Group 2 Innate Lymphoid Cells Link Allergic Lung Inflammation and Liver Immunity

Abstract

Group 2 innate lymphoid cells (ILC2s) are tissue resident in the lung and activated by inhaled allergens via epithelial-derived alarmins including IL-33. Activated ILC2s proliferate, produce IL-5 and IL-13, and induce eosinophilic inflammation. Here, we report that intranasal IL-33 or the protease allergen papain administration resulted in increased numbers of ILC2s not only in the lung but also in peripheral blood and liver. Analyses of IL-33 treated parabiosis mice showed that the increase in lung ILC2s was due to proliferation of lung resident ILC2s, whereas the increase in liver ILC2s was due to the migration of activated lung ILC2s. Lung-derived ILC2s induced eosinophilic hepatitis and expression of fibrosis-related genes. Intranasal IL-33 pre-treatment also attenuated concanavalin A-induced acute hepatitis and cirrhosis. These results suggest that activated lung resident ILC2s emigrate from the lung, circulate, settle in the liver and promote type 2 inflammation and attenuate type 1 inflammation.

Tissue Resident and Migratory Group 2 Innate Lymphoid Cells

“…Moro et al also reported local expansion of tissue resident ILC2s in fat-associated lymphoid clusters (FALC), lung and bronchoalveolar lavage fluid (BALF) during respiratory inflammation induced by intratracheal IL-33 administration into parabiotic mice (4). Many other groups also used parabiosis models and confirmed ILC2 tissue residency at homeostasis and during inflammation (5)(6)(7)(8).…”

“…In the human system, helper ILCs, including ILC2s, are underrepresented in the non-mucosal compared to the mucosal tissues due to the abundance of NK cells, similar to mice (19). However, ILC2s are relatively rare in human SI (20), whereas they are one of the major ILC populations in mouse SI (8,21).…”

Types of necroinflammation, the effect of cell death modalities on sterile inflammation

“…Tissue-resident ILC2s in the lung are activated by inhaled allergens via epithelial-derived IL-33. Furthermore, intranasal IL-33 administration increased the numbers of ILC2s in the lung, also in peripheral blood and in the liver [ 74 ].…”

Immune Checkpoints and Innate Lymphoid Cells—New Avenues for Cancer Immunotherapy

“…Tissue resident ILC act as local gatekeepers to maintain immunological balance and tissue homeostasis. Although tissue compartmentalization occurs at steady state [ 59 , 60 , 61 , 62 , 63 ], non-NK cell ILC are able to traffic between organs in a tissue and subset-dependent manner upon inflammatory perturbations [ 61 , 62 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. This ability of ILC to migrate to other organs ensures that appropriate immune cells are distributed properly to constrain insults and tissue damage within the body.…”

“…Early post-infection blood ILC2 were mainly derived from the small intestine and these cells were progressively replaced by lung-derived ILC2 during the course of infection. In addition, intranasal administrations of IL-33 or papain promoted ILC2 migration through the blood stream to the liver [ 70 ]. These findings indicate that local tissue perturbations induce systemic ILC2 migration and type 2 inflammation.…”