{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:12:42Z","timestamp":1792653162480,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T00:00:00Z","timestamp":1653868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Type 2 Innate lymphoid cells (ILC2s) are tissue-resident immune cells activated by epithelial-derived alarmins upon tissue damage. They regulate immunity against helminth parasites and allergies by expressing type 2 immune response cytokines including IL-9, known to be critical for inducing and potentiating the immune response in such context. Although ILC2s are reported to be the main source of IL-9 in mice during <jats:italic>N. brasiliensis<\/jats:italic> infection, the mechanisms that regulate the expression of IL-9 in these cells are yet to be described. Recent studies have shown that in addition to cytokines, multiple molecules can differentially modulate the functions of ILC2s in various contexts both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Among these stimuli are lipid mediators and neuropeptides, which activate the PKA pathway and have been associated with the regulation of type 2 immune cytokines. In this work we found that ILC2s in mice infected with <jats:italic>N. brasiliensis<\/jats:italic> can be classified into different groups based on the expression of IL-9 and ST2. These distinct populations were distributed in the lung and the small intestine. Through the development of an <jats:italic>in vitro<\/jats:italic> culture system, we sought to determine the stimuli that regulate the expression of these markers in ILC2s. We identified the alarmin IL-33 as being a key player for increased IL-9 expression. Additionally, we found the PKA pathway to be a dual regulator of ILC2 cells, working synergistically with IL-33 to enhance IL-9 production and capable of modulating proliferation and the expression of ILC2 markers. These data provide further evidence of a high heterogeneity between ILC2 subsets in a context dependent manner and calls for careful consideration when choosing the markers to identify these cells <jats:italic>in vivo<\/jats:italic>. Distinguishing ILC2 subsets and dissecting their mechanisms of activation is critical for a deeper understanding of the biology of these cells, allowing their manipulation for therapeutic purposes.<\/jats:p>","DOI":"10.3389\/fimmu.2022.787713","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T07:58:30Z","timestamp":1654070310000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["IL-33 and the PKA Pathway Regulate ILC2 Populations Expressing IL-9 and ST2"],"prefix":"10.3389","volume":"13","author":[{"given":"Enrique","family":"Olgu\u00edn-Mart\u00ednez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofelia","family":"Mu\u00f1oz-Paleta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca E.","family":"Ruiz-Medina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Luis","family":"Ramos-Balderas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ileana","family":"Licona-Lim\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Licona-Lim\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.cyto.2015.05.010","article-title":"T Helper 2 (Th2) Cell Differentiation, Type 2 Innate Lymphoid Cell (ILC2) Development and Regulation of Interleukin-4 (IL-4) and IL-13 Production","volume":"75","author":"Zhu","year":"2015","journal-title":"Cytokine"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a016337","article-title":"Group 2 Innate Lymphoid Cells in Health and Disease","volume":"7","author":"Kim","year":"2015","journal-title":"Cold Spring Harbor Perspect Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nature08636","article-title":". 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