Abstract
Immunological memory has a central role in the adaptive immune systems that can efficiently eliminate pathogens such as virus and bacteria. Particularly, memory CD4 T cells function as a control tower of the adaptive immune systems. However, memory helper T (Th) cells are also involved in the pathogenesis of various chronic inflammatory diseases, including asthma. Recently, we have found IL-5-producing pathogenic population in memory Th2 cells in allergic asthma. We term this population memory-type ‘pathogenic Th2 cells (Tpath2 cells)’ in the airway. Several groups also reported distinct memory type Th2 populations, which produce a large amount of IL-5 or multiple cytokines in addition to IL-4 and IL-13. These populations seem to be responsible for the pathology of chronic inflammatory disorders. Our recent study has revealed that ST2 (a component of IL-33 receptor) expression on Tpath2 cells plays an important role for inducing pathogenicity in memory Th2 cells. Here, we highlight the regulation and function of IL-33 and ST2 on memory Th2 cells, and review their roles in the induction and progression of chronic airway inflammation in both mice and human systems.
Keywords
- Pathogenic Th2 cells (Tpath2 cells)
- Asthma
- IL-33
- IL-5
- ST2
- p38 signal
- Chronic rhinosinusitis (CRS)
- Eosinophilic CRS (ECRS)
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References
Besnard AG, Togbe D, Guillou N, Erard F, Quesniaux V, Ryffel B (2011) IL-33-activated dendritic cells are critical for allergic airway inflammation. Eur J Immunol 41:1675–1686
Christianson CA, Alam R (2013) Mechanisms of sustained signaling in asthma. Curr Opin Allergy Clin Immunol 1:100–105
Cohn L et al (2004) Asthma: mechanisms of disease persistence and progression. Annu Rev Immunol 22:789–815
Coyle AJ, Lloyd C, Tian J, Nguyen T, Erikkson C, Wang L, Ottoson P, Persson P, Delaney T, Lehar S et al (1999) Crucial role of the interleukin 1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses. J Exp Med 190:895–902
Endo Y, Iwamura C, Kuwahara M, Suzuki A, Sugaya K, Tumes DJ, Tokoyoda K, Hosokawa H, Yamashita M, Nakayama T (2011) Eomesodermin controls interleukin-5 production in memory T helper 2 cells through inhibition of activity of the transcription factor GATA3. Immunity 35:733–745
Endo Y, Hirahara K, Yagi R, Nakayama T (2014) Pathogenic memory type Th2 cells in allergic inflammation. Trends Immunol 35:69–78
Endo Y, Hirahara K, Iinuma T, Shinoda K, Tumes DJ, Asou HK, Matsugae N, Obata-Ninomiya K, Yamamoto H, Motohashi S, Oboki K, Nakae S, Saito H, Okamoto Y, Nakayama T (2015) The Interleukin-33-p38 kinase axis confers memory T helper 2 cell pathogenicity in the airway. Immunity 42:294–308
Fort MM et al (2001) IL-25 induces IL-4, IL-5, and IL-13 and Th2-Associated pathologies in vivo. Immunity 15:985–995
Gelfand EW, Kraft M (2009) The importance and features of the distal airways in children and adults. J Allergy Clin Immunol 124:S84–S87
Gevaert P, Lang-Loidolt D, Lackner A, Stammberger H, Staudinger H, Van Zele T, Holtappels G, Tavernier J, van Cauwenberge P, Bachert C (2006) Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps. J Allergy Clin Immunol 118:1133–1141
Gor DO, Rose NR, Greenspan NS (2003) TH1-TH2: a procrustean paradigm. Nat Immunol 4:503–505
Gregory LG, Lloyd CM (2011) Orchestrating house dust mite-associated allergy in the lung. Trends Immunol 32:402–411
Grotenboer NS, Ketelaar ME, Koppelman GH, Nawijn MC (2013) Decoding asthma: translating genetic variation in IL33 and IL1RL1 into disease pathophysiology. J Allergy Clin Immunol 131:856–865
Halim TY, Krauss RH, Sun AC, Takei F (2012) Lung natural helper cells are a critical source of Th2 cell-type cytokines in protease allergen-induced airway inflammation. Immunity 36:451–463
Hamilos DL (2011) Chronic rhinosinusitis: epidemiology and medical management. J Allergy Clin Immunol 128:693–707, quiz 708–699
Holt PG et al (2009) Pathogenic mechanisms of allergic inflammation: atopic asthma as a paradigm. Adv Immunol 104:51–113
Iinuma T, Okamoto Y, Yamamoto H, Inamine-Sasaki A, Ohki Y, Sakurai T, Funakoshi U, Yonekura S, Sakurai D, Hirahara K, Nakayama T (2015) Interleukin-25 and mucosal T cells in noneosinophilic and eosinophilic chronic rhinosinusitis. Ann Allergy Asthma Immunol 114:289–298
Kim HY et al (2010) The many paths to asthma: phenotype shaped by innate and adaptive immunity. Nat Immunol 11:577–584
Kurowska-Stolarska M, Kewin P, Murphy G, Russo RC, Stolarski B, Garcia CC, Komai-Koma M, Pitman N, Li Y, Niedbala W et al (2008) IL-33 induces antigen-specific IL-5+ T cells and promotes allergic-induced airway inflammation independent of IL-4. J Immunol 181:4780–4790
Liew FY, Pitman NI, McInnes IB (2010) Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol 10:103–110
Liu X, Li M, Wu Y, Zhou Y, Zeng L, Huang T (2009) Anti-IL-33 antibody treatment inhibits airway inflammation in a murine model of allergic asthma. Biochem Biophys Res Commun 386:181–185
Lloyd CM (2010) IL-33 family members and asthma – bridging innate and adaptive immune responses. Curr Opin Immunol 22:800–806
Lloyd CM, Hessel EM (2010) Functions of T cells in asthma: more than just T(H)2 cells. Nat Rev Immunol 10:838–848
Oboki K, Ohno T, Kajiwara N, Arae K, Morita H, Ishii A, Nambu A, Abe T, Kiyonari H, Matsumoto K et al (2010) IL-33 is a crucial amplifier of innate rather than acquired immunity. Proc Natl Acad Sci U S A 107:18581–18586
Petersen BC, Budelsky AL, Baptist AP, Schaller MA, Lukacs NW (2012) IL-25 induces type 2 cytokine production in a novel, steroid resistant IL-17RB+ myeloid population that exacerbates asthmatic pathology. Nat Med 18:751–758
Porter PC et al (2011) Seeking common pathophysiology in asthma, atopy and sinusitis. Trends Immunol 32:43–49
Prefontaine D, Nadigel J, Chouiali F, Audusseau S, Semlali A, Chakir J, Martin JG, Hamid Q (2010) Increased IL-33 expression by epithelial cells in bronchial asthma. J Allergy Clin Immunol 125:752–754
Rosenberg HF et al (2013) Eosinophils: changing perspectives in health and disease. Nat Rev Immunol 13:9–22
Scanlon ST, McKenzie AN (2012) Type 2 innate lymphoid cells: new players in asthma and allergy. Curr Opin Immunol 24:707–712
Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X et al (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23:479–490
Szab OSH, Sullivan BM, Peng SL, Glimcher LH (2003) Molecular mechanisms regulating Th1 immune responses. Annu Rev Immunol 21:713–758
Van Bruaene N, Perez-Novo CA, Basinski TM, Van Zele T, Holtappels G, De Ruyck N, Schmidt-Weber C, Akdis C, Van Cauwenberge P, Bachert C, Gevaert P (2008) T-cell regulation in chronic paranasal sinus disease. J Allergy Clin Immunol 121:1435–1441, 1441 e1431–1433
Wang YH et al (2010) A novel subset of CD4(+) T(H)2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma. J Exp Med 207:2479–2491
Zhang N, Van Zele T, Perez-Novo C, Van Bruaene N, Holtappels G, DeRuyck N, Van Cauwenberge P, Bachert C (2008) Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease. J Allergy Clin Immunol 122:961–968
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Endo, Y. et al. (2016). Human and Mouse Memory-Type Pathogenic Th2 (Tpath2) Cells in Airway Inflammation. In: Miyasaka, M., Takatsu, K. (eds) Chronic Inflammation. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56068-5_31
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DOI: https://doi.org/10.1007/978-4-431-56068-5_31
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