Lung ILC2s link innate and adaptive responses in allergic inflammation

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Lung ILC2s link innate and adaptive responses in allergic inflammation Itziar Martinez-Gonzalez, Catherine A. Steer, Fumio Takei Trends in Immunology Volume 36, Issue 3, Pages 189-195 (March 2015) DOI: 10.1016/j.it.2015.01.005 Copyright © 2015 Elsevier Ltd Terms and Conditions

Figure 1 Stimulation of group 2 innate lymphoid cells (ILC2s) by epithelium-derived cytokines leading to innate type 2 immunity. Inhaled allergens induce the release of the alarmins IL-33 and uric acid as well as the secretion of IL-25 and TSLP by the lung epithelium. IL-33 release may be promoted by PAR activation or by uric acid. Epithelial cells also produce IL-25, TSLP, and IL-7. IL-33 stimulates basophils to produce IL-4. Lung ILC2s are stimulated by combinations of IL-33, TSLP, IL-7, and IL-4 and produce type 2 cytokines including IL-5, IL-13, IL-9, and amphiregulin. These cytokines act on different types of cells promoting type 2 lung inflammation characterized by eosinophilia, mucus production, smooth muscle contraction, and airway hyper-reactivity. Abbreviations: AREG, amphiregulin; IgE, immunoglobulin E; IL, interleukin; PAR, protease-activated receptor; TSLP, thymic stromal lymphopoietin. Trends in Immunology 2015 36, 189-195DOI: (10.1016/j.it.2015.01.005) Copyright © 2015 Elsevier Ltd Terms and Conditions

Figure 2 Lung group 2 innate lymphoid cells (ILC2s) promote Th2 cell differentiation. Upon allergen activation, lung ILC2s produce IL-13, which promotes activated CD40+ dendritic cell (DC) migration to the draining mediastinal lymph node (mLN). DCs present antigen to naive CD4+ T cells and drive their differentiation into Th2 cells. Th2 cells then migrate to the lung and produce type 2 cytokines such as IL-4, IL-5, and IL-13 and induce allergic lung inflammation. Abbreviations: aDC, activated dendritic cell; iDC, immature dendritic cell; IL, interleukin; MHCII, major histocompatibility complex class II; mLN, mediastinal lymph node; TCR, T cell receptor; Th2, T helper type 2. Trends in Immunology 2015 36, 189-195DOI: (10.1016/j.it.2015.01.005) Copyright © 2015 Elsevier Ltd Terms and Conditions