{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:38:53Z","timestamp":1784133533337,"version":"3.55.0"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T00:00:00Z","timestamp":1525046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["26221305"],"award-info":[{"award-number":["26221305"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["17K08876"],"award-info":[{"award-number":["17K08876"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development, AMED","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,10,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The lungs are the primary organs of the respiratory system in many animals and have unique epithelial barrier systems to protect the host from continuous invasion of various harmful particles, such as viruses and bacteria. IL-33, a member of the IL-1 family of cytokines, is released from epithelial cells in the mucosal organs and drives the type 2 immune response by activating a number of immune cells in cases of helminth infection. However, IL-33 derived from epithelial cells also causes various allergic diseases via the activation of ST2-positive immune cells, including memory-type (CD62LlowCD44hi) ST2+CD4+ T cells in the lung. Recent studies have revealed that the type 2 inflammation induced by IL-33 is steroid resistant. Steroid resistance causes severe chronic inflammatory diseases, such as intractable asthma. In this review, we will discuss the impact of ST2+CD4+ T cells on shaping the pathology of IL-33-induced eosinophilic inflammation. We will also highlight the mechanism underlying steroid resistance in eosinophilic pneumonia. A better understanding of the cellular and molecular mechanisms underlying steroid resistance is crucial for the development of new therapeutic strategies for intractable allergic diseases.<\/jats:p>\n               <jats:p>Review on the impact of IL-33 in the development of eosinophilic lung inflammation and the mechanism of steroid resistance in the airway inflammation.<\/jats:p>","DOI":"10.1002\/jlb.mr1117-456r","type":"journal-article","created":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T20:44:31Z","timestamp":1525121071000},"page":"895-901","source":"Crossref","is-referenced-by-count":20,"title":["The pathogenicity of IL-33 on steroid-resistant eosinophilic inflammation via the activation of memory-type ST2+CD4+ T cells"],"prefix":"10.1093","volume":"104","author":[{"given":"Kiyoshi","family":"Hirahara","sequence":"first","affiliation":[{"name":"Department of Immunology, Chiba University , Chiba, Japan"},{"name":"AMED-PRIME, AMED , Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Mato","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Jichi Medical University , Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Hagiwara","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Jichi Medical University , Tochigi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinori","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Immunology, Chiba University , Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,4,30]]},"reference":[{"key":"2023032406063059600_jlb10157-cit-0001","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.immuni.2005.09.015","article-title":"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","volume":"23","author":"Schmitz","year":"2005","journal-title":"Immunity"},{"key":"2023032406063059600_jlb10157-cit-0002","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0014-5793(93)81333-U","article-title":"Presence of a novel primary response gene ST2L, encoding a product highly similar to the interleukin 1 receptor type 1","volume":"318","author":"Yanagisawa","year":"1993","journal-title":"FEBS Lett"},{"key":"2023032406063059600_jlb10157-cit-0003","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nri.2016.95","article-title":"Interleukin-33 in health and disease","volume":"16","author":"Liew","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"2023032406063059600_jlb10157-cit-0004","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.immuni.2015.06.006","article-title":"Interleukin-33 in tissue homeostasis, injury, and inflammation","volume":"42","author":"Molofsky","year":"2015","journal-title":"Immunity"},{"key":"2023032406063059600_jlb10157-cit-0005","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.immuni.2015.01.016","article-title":"The interleukin-33-p38 kinase axis confers memory T helper 2 cell pathogenicity in the airway","volume":"42","author":"Endo","year":"2015","journal-title":"Immunity"},{"key":"2023032406063059600_jlb10157-cit-0006","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1146\/annurev-immunol-051116-052350","article-title":"Th2 cells in health and disease","volume":"35","author":"Nakayama","year":"2017","journal-title":"Annu Rev Immunol"},{"key":"2023032406063059600_jlb10157-cit-0007","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/j.0105-2896.2006.00413.x","article-title":"The regulation of allergy and asthma","volume":"212","author":"Umetsu","year":"2006","journal-title":"Immunol Rev"},{"key":"2023032406063059600_jlb10157-cit-0008","doi-asserted-by":"crossref","first-page":"E2842","DOI":"10.1073\/pnas.1512600113","article-title":"Thy1+IL-7+ lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation","volume":"113","author":"Shinoda","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023032406063059600_jlb10157-cit-0009","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1056\/NEJM196904102801501","article-title":"Chronic eosinophilic pneumonia","volume":"280","author":"Carrington","year":"1969","journal-title":"N Engl J Med"},{"key":"2023032406063059600_jlb10157-cit-0010","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1056\/NEJM198908313210903","article-title":"Acute eosinophilic pneumonia as a reversible cause of noninfectious respiratory failure","volume":"321","author":"Allen","year":"1989","journal-title":"N Engl J Med"},{"key":"2023032406063059600_jlb10157-cit-0011","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1378\/chest.103.1.162","article-title":"Chronic eosinophilic pneumonia. 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