Pulmonary environmental cues drive group 2 innate lymphoid cell dynamics in mice and humans

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Science Immunology  07 Jun 2019:
Vol. 4, Issue 36, eaav7638
DOI: 10.1126/sciimmunol.aav7638

Filming the airways

Group 2 innate lymphoid cells (ILC2s) are key drivers of immune responses in the lung. Using an interleukin-13 (IL-13) reporter mouse strain in conjunction with sophisticated microscopy, Puttur et al. have visualized migration of ILC2s in allergic airway inflammation. They report that ILC2s exhibit dynamic ameboid-like movement in response to IL-33 and that IL-33–induced up-regulation of chemokine receptor 8 on ILC2s promotes homing of ILC2s to deposits of chemokine ligand 8 within the airways. They also found a role for collagen-I, a component of the extracellular matrix (ECM) in directly regulating migration of ILC2s. The study underscores the importance of how structural cues from the ECM work in conjunction with immune mediators to influence immune cell functions in tissues.


Group 2 innate lymphoid cells (ILC2s) are enriched in mucosal tissues (e.g., lung) and respond to epithelial cell–derived cytokines initiating type 2 inflammation. During inflammation, ILC2 numbers are increased in the lung. However, the mechanisms controlling ILC2 trafficking and motility within inflamed lungs remain unclear and are crucial for understanding ILC2 function in pulmonary immunity. Using several approaches, including lung intravital microscopy, we demonstrate that pulmonary ILC2s are highly dynamic, exhibit amoeboid-like movement, and aggregate in the lung peribronchial and perivascular spaces. They express distinct chemokine receptors, including CCR8, and actively home to CCL8 deposits located around the airway epithelium. Within lung tissue, ILC2s were particularly motile in extracellular matrix–enriched regions. We show that collagen-I drives ILC2 to markedly change their morphology by remodeling their actin cytoskeleton to promote environmental exploration critical for regulating eosinophilic inflammation. Our study provides previously unappreciated insights into ILC2 migratory patterns during inflammation and highlights the importance of environmental guidance cues in the lung in controlling ILC2 dynamics.

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