ILC2-derived LIF licences progress from tissue to systemic immunity

Abstract Migration and homing of immune cells are critical for immune surveillance. Trafficking is mediated by combinations of adhesion and chemokine receptors that guide immune cells, in response to chemokine signals, to specific locations within tissues and the lymphatic system to support tissue-l...

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Bibliographic Details
Published in:Nature (London) 2024-08, Vol.632 (8026), p.885-892
Main Authors: Gogoi, Mayuri, Clark, Paula A., Ferreira, Ana C. F., Rodriguez Rodriguez, Noe, Heycock, Morgan, Ko, Michelle, Murphy, Jane E., Chen, Victor, Luan, Shi-Lu, Jolin, Helen E., McKenzie, Andrew N. J.
Format: Article
Language:English
Subjects:
Allergens
Allergies
Bioaccumulation
Bone marrow
Cell migration
Chemokine receptors
Chemokines
Chronic infection
Cytokines
Dendritic cells
Endothelial cells
Homing
Homing behavior
Immune system
Immunity
Immunity (Disease)
Immunosurveillance
Infections
Inflammation
Influenza
Leukemia
Leukemia inhibitory factor
Lungs
Lymph nodes
Lymphatic system
Lymphocytes
Lymphoid cells
Tissues
Viral infections
Viruses
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Summary:Abstract Migration and homing of immune cells are critical for immune surveillance. Trafficking is mediated by combinations of adhesion and chemokine receptors that guide immune cells, in response to chemokine signals, to specific locations within tissues and the lymphatic system to support tissue-localized immune reactions and systemic immunity 1,2 . Here we show that disruption of leukaemia inhibitory factor (LIF) production from group 2 innate lymphoid cells (ILC2s) prevents immune cells leaving the lungs to migrate to the lymph nodes (LNs). In the absence of LIF, viral infection leads to plasmacytoid dendritic cells (pDCs) becoming retained in the lungs where they improve tissue-localized, antiviral immunity, whereas chronic pulmonary allergen challenge leads to marked immune cell accumulation and the formation of tertiary lymphoid structures in the lung. In both cases immune cells fail to migrate to the lymphatics, leading to highly compromised LN reactions. Mechanistically, ILC2-derived LIF induces the production of the chemokine CCL21 from lymphatic endothelial cells lining the pulmonary lymphatic vessels, thus licensing the homing of CCR7 + immune cells (including dendritic cells) to LNs. Consequently, ILC2-derived LIF dictates the egress of immune cells from the lungs to regulate tissue-localized versus systemic immunity and the balance between allergen and viral responsiveness in the lungs.
ISSN:0028-0836
1476-4687
1476-4687
DOI:10.1038/s41586-024-07746-w