title: Overexpression of hypoxia-inducible factor 1 alpha impacts FoxP3 levels in mycosis fungoides--cutaneous T-cell lymphoma: clinical implications.
abstract: Mycosis fungoides (MF) is the most common variant of primary cutaneous T-cell lymphoma, and decreased forkhead box P3 (FoxP3) expression has been reported in MF late stages. Hypoxia-inducible factor 1 alpha (HIF-1α) may regulate FoxP3 expression; however, it is unknown whether HIF-1α is expressed in the CD4(+) T cells of MF patients and how it could affect the expression of FoxP3. Therefore, we evaluated the expression of HIF-1α and FoxP3 in CD4(+) T cells obtained from the skin lesions of MF patients. We found increased cell proliferation and an increase in CD4(+) T cells with an aberrant phenotype among early stage MF patients. HIF-1α was overexpressed in these CD4(+) T cells. In addition, we found a decrease in the percentage of FoxP3(+) cells both in the skin of MF patients, when compared with control skin samples, and with disease progression. In addition, a negative correlation was established between HIF-1α and FoxP3 expression. Skin HIF-1α expression in MF patients correlated with the extent of the affected area and increased with the disease progression. Finally, we showed that ex vivo inhibition of HIF-1α degradation increases the percentage of FoxP3(+) T cells in skin lesions. Our results suggest that overexpression of HIF-1α affects the levels of FoxP3 in MF patients, which could have relevant implications in terms of disease outcome.
authors.affiliation: Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Instituto Mexicano del Seguro Social, México city, México; Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto, Politécnico Nacional, México city, México.
authors.forename: M
authors.initials: M
authors.lastname: Alcántara-Hernández
authors.forename: C
authors.initials: C
authors.lastname: Torres-Zárate
authors.forename: G
authors.initials: G
authors.lastname: Pérez-Montesinos
authors.forename: F
authors.initials: F
authors.lastname: Jurado-Santacruz
authors.forename: M A
authors.initials: MA
authors.lastname: Domínguez-Gómez
authors.forename: A
authors.initials: A
authors.lastname: Peniche-Castellanos
authors.forename: E
authors.initials: E
authors.lastname: Ferat-Osorio
authors.forename: N
authors.initials: N
authors.lastname: Neri
authors.forename: M J
authors.initials: MJ
authors.lastname: Nambo
authors.forename: I
authors.initials: I
authors.lastname: Alvarado-Cabrero
authors.forename: M
authors.initials: M
authors.lastname: Moreno-Lafont
authors.forename: S
authors.initials: S
authors.lastname: Huerta-Yepez
authors.forename: L C
authors.initials: LC
authors.lastname: Bonifaz
mesh_terms: D018450:Disease Progression; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D016410:Lymphoma, T-Cell, Cutaneous / Q000378:metabolism*; D009182:Mycosis Fungoides / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: FoxP3; cutaneous T-cell lymphoma; hypoxia inducible factor 1 alpha; mycosis fungoides