Grafted Sertoli Cells Exert Immunomodulatory Non-Immunosuppressive Effects in Preclinical Models of Infection and Cancer

The Sertoli cells (SeCs) of the seminiferous tubules secrete a multitude of immunoregulatory and trophic factors to provide immune protection and assist in the orderly development of germ cells. Grafts of naked or encapsulated SeCs have been proved to represent an interesting therapeutic option in a plethora of experimental models of diseases. However, whether SeCs have immunosuppressive or immunomodulatory effects, which is imperative for their clinical translatability, has not been demonstrated. We directly assessed the immunopotential of intraperitoneally grafted microencapsulated porcine SeCs (MC-SeCs) in murine models of fungal infection (Aspergillus fumigatus or Candida albicans) or cancer (Lewis lung carcinoma/LLC or B16 melanoma cells). We found that MC-SeCs (i) provide antifungal resistance with minimum inflammatory pathology through the activation of the tolerogenic aryl hydrocarbon receptor/indoleamine 2,3-dioxygenase pathway; (ii) do not affect tumor growth in vivo; and (iii) reduce the LLC cell metastatic cancer spread associated with restricted Vegfr2 expression in primary tumors. Our results point to the fine immunoregulation of SeCs in the relative absence of overt immunosuppression in both infection and cancer conditions, providing additional support for the potential therapeutic use of SeC grafts in human patients.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

Cells - 13(2024), 6 vom: 19. März

Sprache:

Englisch

Beteiligte Personen:

Chiappalupi, Sara [VerfasserIn]
Salvadori, Laura [VerfasserIn]
Borghi, Monica [VerfasserIn]
Mancuso, Francesca [VerfasserIn]
Pariano, Marilena [VerfasserIn]
Riuzzi, Francesca [VerfasserIn]
Luca, Giovanni [VerfasserIn]
Romani, Luigina [VerfasserIn]
Arato, Iva [VerfasserIn]
Sorci, Guglielmo [VerfasserIn]

Links:

Volltext

Themen:

Fungal infection
Immunomodulation
Immunosuppressive Agents
Journal Article
Metastasis
Sertoli cells
Tumor growth

Anmerkungen:

Date Completed 28.03.2024

Date Revised 29.03.2024

published: Electronic

Citation Status MEDLINE

doi:

10.3390/cells13060544

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM370239385