Sentinels of the Type 2 Immune Response

• Published in: Trends in immunology Vol. 39; no. 2; pp. 99 - 111
• Main Authors: von Moltke, Jakob, Pepper, Marion
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-02-2018; Elsevier Limited
• Subjects: Animals; Cellular Microenvironment; Cytokines; Food allergies; Homeostasis; Humans; Immune response; Immune system; Immunity, Cellular; Immunomodulation; Immunotherapy - methods; Inflammation; Intestines - immunology; Lung - immunology; Lungs; Lymphocytes T; Microorganisms; Parasites; Pattern recognition; Replicating; Small intestine; Smooth muscle; T cell receptors; T-Lymphocyte Subsets - immunology; Th1 Cells - immunology; Th2 Cells - immunology; Tissues
• ISSN: 1471-4906; 1471-4981; 1471-4981
• DOI: 10.1016/j.it.2017.10.004

Type 2 immune responses have evolved to sense and respond to large, non-replicating infections or non-microbial noxious compounds in tissues. The development of these responses therefore depends upon highly coordinated and tightly regulated tissue-residing cellular sensors and responders. Multiple exposure to type 2 helper T cell (Th2)-inducing stimuli further enhances both the diversity and potency of the response. This review discusses advances in our understanding of the interacting cellular subsets that comprise both primary and secondary type 2 responses. Current knowledge regarding type 2 immune responses in the lung are initially presented and are then contrasted with what is known about the small intestine. The studies described portray an immune response that depends upon well-organized tissue structures, and suggest their modulation as a therapeutic strategy.
Non-hematopoietic cells of the lung epithelium, nervous system, and stroma are the primary sentinels of type 2 inducers such as allergens and helminths.
Group 2 innate lymphoid cells integrate signals from non-hematopoietic cells, and release cytokines to drive the downstream type 2 inflammatory response and perhaps adaptive type 2 immunity.
Once antigen-specific responses are established, tissue-resident CD4 memory T cells and B cells, together with IgE-loaded mast cells, become the dominant type 2 sentinels in the lung.
Tertiary lymphoid structures develop in the lung with exposure, and these provide an important site for the maintenance and perhaps even priming of adaptive immune cells.