Type 2 immunity: Expanding our view

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Science Immunology  06 Jul 2018:
Vol. 3, Issue 25, eaat1604
DOI: 10.1126/sciimmunol.aat1604


  • Fig. 1 A timeline of discoveries in TH2 immune responses.

    Since the identification of a TH2-specific cytokine profile by Mosmann and colleagues (112), a series of seminal discoveries have continued to advance the field of type 2 immunity. In more recent years, there has been fresh impetus in the field coinciding with the identification of ILC2s; an increasing awareness of how diverse exogenous stimuli can trigger type 2 responses and the importance of these responses in a broad biological processes, such as repair, remodeling, and regulation of metabolic homeostasis.

  • Fig. 2 ILC2s sense microenvironmental cues to elicit a type 2 response.

    Lung-resident cells function as specialized tissue sentinels to detect a broad array of stimuli, including allergens, specific viruses, bacteria, or general host perturbations away from a homeostatic basal state. Subsequently, these sensors release a disparate set of mediators, including IL-25, TSLP, IL-33, TL1A, leukotrienes (LTs), prostaglandins (PGs), and neuropeptides VIP and NMU. These mediators converge to activate ILC2s, which produce IL-5, IL-13, and IL-9 and so function as a fundamental decision-maker in bridging tissue perturbation and induction of a TH2 response. ECM, extracellular matrix.

  • Fig. 3 Type 2 immunity contributes to both homeostatic and pathologic processes.

    Cells associated with type 2 immunity—eosinophils, ILC2, and alternatively activated macrophages (AAMs)—are important for basic metabolic processes required to maintain thermostatic and metabolic homeostasis and to drive pathology during allergic disease and facilitate clearance of parasitic worms. These individual processes seem to be distinguished by virtue of the adaptive cells involved. Treg cells influence maintenance of homeostasis, whereas different effector T cell subsets direct the nuances of pathological immune reactions.

  • Fig. 4 Broadening our view of type 2 immune reactions.

    The discovery of ILC2s has radically changed our view of type 2 responses as a process that regulates immunity to allergens and helminths into one of a vital rheostat for maintenance and restoration of homeostasis after environmental stimuli. The ability of ILC2 to sense the local environment and interact with a panoply of immune and stromal cells enables them to take center stage in the fight to maintain health and prevent disease. ATP, adenosine 5′-triphosphate; GM-CSF, granulocyte-macrophage colony-stimulating factor; LPA, lysophosphatidic acid; ROS, reactive oxygen species.