Pathological inflammatory memories
Kiyoshi Hirahara
Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan
Trauma, infection with various pathogenic pathogens, autoimmunity, and ischemic injury cause tissue damage and tissue inflammation. Previously inflamed tissues store “inflammatory memories” that cause prolonged inflammation as well as irreversible remodeling of inflamed tissue. In particular, the storage of these pathological inflammatory memories drives chronic inflammation, which induces subsequent organ dysfunction. An integrated understanding of the mechanisms underlying the creation of inflammatory memories is required for the establishment of next-generation therapies for intractable diseases; however, it is difficult to grasp the whole picture of the machinery involved in inflammatory memories because a number of different cells that comprise these tissues, including stromal cells, epithelial cells, neurons, and immune cells, play roles in the process.
In this seminar, I will focus on chronic airway inflammation as a model of inflammatory disease that causes the induction of “inflammatory memories”. I would like to introduce our finding regarding ectopic lymphoid-like structures called inducible bronchus-associated lymphoid tissue (iBALT), which are formed during chronic allergic inflammation in the lung. Importantly, iBALT is a key structure for the maintenance of memory-type pathogenic helper T cells that drive immune-related pathology, including chronic lung inflammation such as asthma. Furthermore, our recent research progress has shed light on the heterogeneity of memory-type pathogenic T cells; that is, the IL-5-producing memory-type Tpath2 subset is critical for the recruitment and differentiation of eosinophils in allergic airway inflammation, while Amphiregulin-producing Tpath2 cells are critical for the induction of fibrotic changes. In the case of chronic allergic conjunctivitis, we recently identified CGRP-expressing Tpath2 cells that induce severe itching.
In order to develop new therapeutic strategies for intractable allergic diseases, it will become increasingly important to understand the precise features of Tpath cells.
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