ICAM-1 controls development and function of ILC2

AH Lei, Q Xiao, GY Liu, K Shi, Q Yang, X Li… - Journal of Experimental …, 2018 - rupress.org
AH Lei, Q Xiao, GY Liu, K Shi, Q Yang, X Li, YF Liu, HK Wang, WP Cai, YJ Guan…
Journal of Experimental Medicine, 2018rupress.org
Group 2 innate lymphoid cells (ILC2s) are emerging as key players in the pathogenesis of
allergic airway inflammation. The mechanisms regulating ILC2, however, are not fully
understood. Here, we found that ICAM-1 is required for the development and function of
ILC2. ICAM-1–deficient (ICAM-1−/−) mice displayed significantly lower levels of ILC2s in the
bone marrow and peripheral tissues than wild-type controls. CLP transfer and in vitro culture
assays revealed that the regulation of ILC2 by ICAM-1 is cell intrinsic. Furthermore, ILC2s …
Group 2 innate lymphoid cells (ILC2s) are emerging as key players in the pathogenesis of allergic airway inflammation. The mechanisms regulating ILC2, however, are not fully understood. Here, we found that ICAM-1 is required for the development and function of ILC2. ICAM-1–deficient (ICAM-1−/−) mice displayed significantly lower levels of ILC2s in the bone marrow and peripheral tissues than wild-type controls. CLP transfer and in vitro culture assays revealed that the regulation of ILC2 by ICAM-1 is cell intrinsic. Furthermore, ILC2s from ICAM-1−/− mice were functionally impaired, as indicated by the diminished production of type-2 cytokines in response to IL-33 challenge. The reduction in lung ILC2s caused a clear remission of airway inflammation in ICAM-1−/− mice after administration of papain or Alternaria alternata. We further demonstrate that ILC2 defects caused by ICAM-1 deficiency are due to ERK signaling-dependent down-regulation of GATA3 protein. Collectively, these observations identify ICAM-1 as a novel regulator of ILC2.
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