{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T04:54:44Z","timestamp":1776401684289,"version":"3.51.2"},"reference-count":0,"publisher":"Association of Basic Medical Sciences of FBIH","issue":"1","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomol Biomed"],"abstract":"<jats:p>Amphiregulin (AREG)\/epidermal growth factor receptor (EGFR) signaling induces hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1), leading to promotion of T helper 9 (Th9) differentiation and anti-tumor functions. However, the role of the AREG\/EGFR\/HIF-1\u03b1 pathway in regulating interleukin-9 (IL-9) production by T cells in adult patients with infectious mononucleosis (IM) has not been fully elucidated. Fifty IM patients and 20 controls were enrolled. The percentages of Th9 and T cytotoxic 9 (Tc9) cells, the mRNA relative expressions of the transcription factors of IL-9-secreting T cells, purine-rich nucleic acid binding protein 1 (PU.1) and forkhead box protein O1 (FOXO1), and the levels of IL-9, AREG, EGFR, and HIF-1\u03b1 were measured. Peripheral blood mononuclear cells from IM patients were stimulated with EGFR inhibitor or exogenous AREG in the presence or absence of anti-HIF-1\u03b1. Regulation of the AREG\/EGFR\/HIF-1\u03b1 pathway to IL-9 production by T cells was assessed. The percentages of Th9 and Tc9 cells, plasma IL-9 levels, and PU.1 and FOXO1 mRNA expressions were elevated in IM patients. Plasma levels of AREG and HIF-1\u03b1 were also increased in IM patients. AREG levels correlated positively with the percentages of Th9 and Tc9 cells in IM patients. Inhibition of EGFR suppressed IL-9-producing T cell differentiation and HIF-1\u03b1 production. Exogenous AREG stimulation not only induced EGFR and HIF-1\u03b1 expression but also promoted IL-9-secreting T cell differentiation. Neutralization of HIF-1\u03b1 abrogated AREG\/EGFR-induced Th9 and Tc9 differentiation in IM patients. The current data suggested that the AREG\/EGFR\/HIF-1\u03b1 pathway contributed to the elevation of Th9 and Tc9 differentiation in IM patients.<\/jats:p>","DOI":"10.17305\/bjbms.2022.8013","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T16:51:15Z","timestamp":1663865475000},"page":"63-72","source":"Crossref","is-referenced-by-count":3,"title":["Amphiregulin\/epidermal growth factor receptor\/hypoxia-inducible factor-1\u03b1 pathway regulates T helper 9 and T cytotoxic 9 cell response in adult patients with infectious mononucleosis"],"prefix":"10.17305","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1949-7737","authenticated-orcid":false,"given":"Yu","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9044-4240","authenticated-orcid":false,"given":"Ying","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"6922","published-online":{"date-parts":[[2023,1,6]]},"container-title":["Biomolecules and Biomedicine"],"original-title":[],"link":[{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/8013\/2602","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/8013\/2602","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T23:01:11Z","timestamp":1772233271000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/view\/8013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,6]]},"references-count":0,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1,6]]}},"URL":"https:\/\/doi.org\/10.17305\/bjbms.2022.8013","relation":{},"ISSN":["2831-090X","2831-0896"],"issn-type":[{"value":"2831-090X","type":"electronic"},{"value":"2831-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2023,1,6]]}}}