Title:

Pathogenic Th2 cells (Tpath2 cells) in chronic allergic airway inflammation.

 

Toshinori Nakayama
Affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, and CREST-AMED, AMED, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan

 

Abstract:
To develop more effective vaccines and strategies to regulate chronic inflammatory diseases, it is important to understand the mechanisms underlying the generation and maintenance of immunological memory. In 2011, we identified a highly pathogenic IL-5-producing memory Th2 cell subset in allergic airway inflammation (Endo et al. Immunity, 2011). Based on these data, we propose a new model called “Pathogenic Th population disease induction model” in the pathogenesis of Th1/Th2/Th17 diseases (Endo et al. Trends in Immunology, 2014). We have extended our research, and found that the pathogenic Th2 cells (Tpath2 cells) are a distinct cell population generated in vivo, and express high levels of IL-33 receptor component, ST2. We have investigated how Tpath2 cells are induced, and found that interleukin-33 (IL-33)-ST2 signals play a crucial role and selectively licenses memory Th2 cells to induce allergic airway inflammation via production of IL-5, and that the p38 MAP kinase pathway is a central downstream target of IL-33-ST2 in both mouse and human memory Th2 cells. In addition, we found that IL-33 induced upregulation of IL-5 by human memory CD4+ T cells isolated from nasal polyps of eosinophilic chronic rhinosinusitis patients. Therefore, IL-33-ST2-p38 signaling appears to directly instruct memory Th2 cells to become Tpath2 cells that produce huge amount of IL-5 and induce eosinophilic inflammation in the airway (Endo et al. Immunity, 2015). These newly identified memory type Tpath2 cells are CD44+ CD62Llo CXCR3lo CCR4+ CCR8+ IL-7Rα+ ST2+ CD4 T cells. In addition, how Tpath 2 cells are maintained in the lung will be discussed (Shinoda et al. PNAS in press).