Open AccessAmphiregulin/epidermal growth factor receptor/hypoxia inducible factor-1α pathway regulates T helper 9 and T cytotoxic 9 cell response in adult patients with infectious mononucleosis
Author(s) -
Yu Li,
Lan Li,
Weihua Zhang,
Ying Gao
Publication year - 2022
Publication title -
bosnian journal of basic medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 25
eISSN - 1840-4812
pISSN - 1512-8601
DOI - 10.17305/bjbms.2022.8013
Subject(s) - amphiregulin , cytotoxic t cell , epidermal growth factor receptor , medicine , endocrinology , interleukin 2 , peripheral blood mononuclear cell , t cell , cancer research , biology , interleukin , epidermal growth factor , immunology , receptor , immune system , cytokine , in vitro , biochemistry
Amphiregulin (AREG)/epidermal growth factor receptor (EGFR) signaling induces hypoxia-inducible factor-1α (HIF-1α), leading to promotion of T helper 9 (Th9) differentiation and anti-tumor functions. However, the role of the AREG/EGFR/HIF-1α 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-1α 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-1α. Regulation of the AREG/EGFR/HIF-1α 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-1α 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-1α production. Exogenous AREG stimulation not only induced EGFR and HIF-1α expression but also promoted IL-9-secreting T cell differentiation. Neutralization of HIF-1α abrogated AREG/EGFR-induced Th9 and Tc9 differentiation in IM patients. The current data suggested that the AREG/EGFR/HIF-1α pathway contributed to the elevation of Th9 and Tc9 differentiation in IM patients.