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Peer-reviewedCC BYBiology

STAT6 Deficiency Accelerates DMBA/TPA-Induced Skin Papilloma Development and Is Associated with Regulatory T-Cell Accumulation and Reduced CD8+IFN-γ+ Responses.

  • Aranza Mejía-Muñoz1
  • Tania Galindo-Santamaría1
  • Valeria Moreno-Tovar1
  • Citlaltepetl Salinas-Lara2,3
  • Carlos Sánchez-Garibay3
  • Rubén D Arroyo Olarte1,2
  • Sonia Leon-Cabrera1,2
  1. 1Unidad de Biomedicina (UBIMED), Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico.
  2. 2Carrera de Médico Cirujano, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico.
  3. 3Neuropatología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico.
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Abstract

Inflammation and the balance between antitumor surveillance and immunoregulatory mechanisms influence chemically induced skin tumor development. STAT6 is a central mediator of IL-4/IL-13 signaling, but its contribution to early skin papilloma development remains unclear. Here, we examined papilloma onset and burden, histopathological alterations, Treg accumulation, and CD8+ T-cell-associated responses in WT and STAT6-deficient mice subjected to a two-stage DMBA/TPA protocol. STAT6-/- mice developed papillomas significantly earlier and exhibited a markedly greater lesion burden than WT mice. This phenotype was associated with more prominent keratinization-related histopathological features, increased Foxp3+ Treg frequency and PD-1 expression in skin-draining lymph nodes, and a broader distribution of Foxp3+ cells within papillomas. STAT6 deficiency was also accompanied by attenuated CD8+IFN-γ+ responses in draining lymph nodes and reduced CD8+ cell infiltration within lesions. Collectively, these findings reveal a distinct immune profile associated with enhanced susceptibility to chemically induced skin papillomas and underscore the context-dependent role of STAT6 in cutaneous tumor immunity.

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Cite

BibTeXRIS
BibTeX
@article{mejiamunoz2026stat6,
  title = {{STAT6 Deficiency Accelerates DMBA/TPA-Induced Skin Papilloma Development and Is Associated with Regulatory T-Cell Accumulation and Reduced CD8+IFN-γ+ Responses.}},
  author = {Aranza Mejía-Muñoz and Tania Galindo-Santamaría and Valeria Moreno-Tovar and Citlaltepetl Salinas-Lara and Carlos Sánchez-Garibay and Rubén D Arroyo Olarte and Sonia Leon-Cabrera},
  journal = {Biology},
  year = {2026},
  month = oct,
  doi = {10.3390/biology15191747},
  url = {https://europepmc.org/article/MED/42883420},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - STAT6 Deficiency Accelerates DMBA/TPA-Induced Skin Papilloma Development and Is Associated with Regulatory T-Cell Accumulation and Reduced CD8+IFN-γ+ Responses.
AU  - Aranza Mejía-Muñoz
AU  - Tania Galindo-Santamaría
AU  - Valeria Moreno-Tovar
AU  - Citlaltepetl Salinas-Lara
AU  - Carlos Sánchez-Garibay
AU  - Rubén D Arroyo Olarte
AU  - Sonia Leon-Cabrera
PY  - 2026
DA  - 2026/10/02
JO  - Biology
DO  - 10.3390/biology15191747
UR  - https://europepmc.org/article/MED/42883420
AB  - Inflammation and the balance between antitumor surveillance and immunoregulatory mechanisms influence chemically induced skin tumor development. STAT6 is a central mediator of IL-4/IL-13 signaling, but its contribution to early skin papilloma development remains unclear. Here, we examined papilloma onset and burden, histopathological alterations, Treg accumulation, and CD8+ T-cell-associated responses in WT and STAT6-deficient mice subjected to a two-stage DMBA/TPA protocol. STAT6-/- mice developed papillomas significantly earlier and exhibited a markedly greater lesion burden than WT mice. This phenotype was associated with more prominent keratinization-related histopathological features, increased Foxp3+ Treg frequency and PD-1 expression in skin-draining lymph nodes, and a broader distribution of Foxp3+ cells within papillomas. STAT6 deficiency was also accompanied by attenuated CD8+IFN-γ+ responses in draining lymph nodes and reduced CD8+ cell infiltration within lesions. Collectively, these findings reveal a distinct immune profile associated with enhanced susceptibility to chemically induced skin papillomas and underscore the context-dependent role of STAT6 in cutaneous tumor immunity.
SN  - 2079-7737
ER  -