{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:52:08Z","timestamp":1792799528994,"version":"4.5.0"},"reference-count":61,"publisher":"American Society for Clinical Investigation","issue":"20","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome Trust CIDRI-Africa","award":["203135Z\/16\/Z)"],"award-info":[{"award-number":["203135Z\/16\/Z)"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"South African National Research Foundation","award":["117721,111946"],"award-info":[{"award-number":["117721,111946"]}]},{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"crossref","award":["416061"],"award-info":[{"award-number":["416061"]}],"id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001646","name":"Robert Bosch Stiftung","doi-asserted-by":"crossref","award":["12.5.F081.0008.0"],"award-info":[{"award-number":["12.5.F081.0008.0"]}],"id":[{"id":"10.13039\/501100001646","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Wellcome Trust CIDRI-Africa","award":["203135Z\/16\/Z)"],"award-info":[{"award-number":["203135Z\/16\/Z)"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,15]]},"abstract":"<jats:p>\n                    Impaired tolerance to innocuous particles during allergic asthma has been linked to increased plasticity of FoxP3\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T cells (Tregs) reprogramming into pathogenic effector cells, thus exacerbating airway disease. However, failure of tolerance mechanisms is driven by Th2 inflammatory signals. Therefore, the in vivo role of canonical IL-4 receptor \u03b1 (IL-4R\u03b1) signaling, an essential driver of Th2-type airway responses to allergens, on the regulatory function of FoxP3\n                    <jats:sup>+<\/jats:sup>\n                    Tregs in allergic asthma was explored. Here, we used transgenic Foxp3\n                    <jats:sup>cre<\/jats:sup>\n                    IL-4R\u03b1\n                    <jats:sup>\u2013\/lox<\/jats:sup>\n                    and littermate control mice to investigate the role of IL-4 and IL-13 signaling via Tregs in house dust mite\u2013induced (HDM-induced) allergic airway disease. We sensitized mice intratracheally on day 0, challenged them on days 6\u201310, and analyzed airway hyperresponsiveness (AHR), airway inflammation, mucus production, and cellular profile on day 14. In the absence of IL-4R\u03b1 responsiveness on FoxP3\n                    <jats:sup>+<\/jats:sup>\n                    Tregs, exacerbated AHR and airway inflammation were shown in HDM-sensitized mice. Interestingly, reduced induction of FoxP3\n                    <jats:sup>+<\/jats:sup>\n                    Tregs accompanied increased IL-33 alarmin production and type 2 innate lymphoid cell activation in the lung, exacerbating airway hyperreactivity and lung eosinophilia. Taken together, our findings indicate that IL-4R\u03b1\u2013unresponsive FoxP3\n                    <jats:sup>+<\/jats:sup>\n                    Tregs result in exaggerated innate Th2-type, IL-33\u2013dependent airway inflammation and a break in tolerance during allergic asthma.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.136206","type":"journal-article","created":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T12:01:46Z","timestamp":1600171306000},"source":"Crossref","is-referenced-by-count":23,"title":["IL-4R\u03b1 signaling in CD4+CD25+FoxP3+ T regulatory cells restrains airway inflammation via limiting local tissue IL-33"],"prefix":"10.1172","volume":"5","author":[{"given":"Jermaine","family":"Khumalo","sequence":"first","affiliation":[{"name":"Division of Immunology, and South African Medical Research Council (SAMRC) Immunology of Infectious Diseases, Department of Pathology,"},{"name":"International Centre for Genetic Engineering and Biotechnology (ICGEB), 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