Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus

Laurel A Monticelli et al., Nat. Immunol. 12:1045–1054, 2011

Speaker: Nai-Huei Jhong (鍾乃惠)                               Time:13:00~14:00, May.30, 2012

Commentator: Dr. Chi-Chang Shieh (謝奇璋老師)     Place: Room 601

Abstract

Innate lymphoid cells (ILCs), which represent a diverse family of hematopoietic immune cells and exhibit heterogeneity in anatomical location and function, are critical regulators of inflammation and immunity¹. Whether ILCs influence immune responses or tissue homeostasis at other mucosal sites remains poorly understood. In this study, the authors investigated a previously unrecognized role for ILCs in promoting the restoration of tissue homeostasis in the lungs with influenza virus infection. First, the authors identified a population of lung-resident ILCs in mice and humans that expressed the alloantigen Thy-1 (CD90), interleukin 2 (IL-2) receptor α-chain (CD25), IL-7 receptor α-chain (CD127) and the IL-33 receptor subunit T1-ST2. Notably, the pulmonary ILC population was demonstrated in repairing airway epithelial integrity and restoring tissue homeostasis following influenza virus infection. Depletion of pulmonary ILCs or blockade of IL-33 signaling led to impaired lung function with a loss of airway epithelial integrity and effective tissue remodeling. Importantly, given the lack of specificity of ILC targeting, reconstitution of ILC-depleted mice with lung ILCs promoted the epithelial restorative capacity. This ILC-mediated repair of airway epithelia appeared to function independently of IL-13. The authors demonstrated via genome-wide profiling that lung ILCs selectively expressed genes associated with wound healing. One such gene encoded amphiregulin, a member of the epidermal growth factor family, which was subsequently demonstrated to be upregulated in the influenza virus-infected lungs. Taken together, these results presented a previously unrecognized role for lung ILCs in promoting airway epithelial integrity and lung tissue homeostasis through the production of amphiregulin. Collectively, targeting ILC responses in the airway and other tissues may offer new therapeutic potential in the clinical management of tissue damage or chronic inflammation.

References

1.          Steven A. Saenz., et al., Innate immune cell populations function as initiators and effectors in Th2 cytokine responses. Trends in Immunology31:407-413, 2010