Banca de QUALIFICAÇÃO: LAURA DE QUADROS PEREIRA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : LAURA DE QUADROS PEREIRA
DATE: 23/10/2023
TIME: 14:00
LOCAL: Auditório 801, Bloco B, Campus Santo André da Universidade Federal do ABC
TITLE:

Enteroendocrine hormones and the immune system cells: impact on metabolism, differentiation and function

PAGES: 63
BIG AREA: Ciências Biológicas
AREA: Imunologia
SUBÁREA: Imunologia Celular
SUMMARY:

Introduction: Enteroendocrine cells are epithelial cells residing in the epithelial layer of the gastrointestinal tract. They become activated in the presence of nutrients, leading to the secretion of hormones. These enteroendocrine hormones (HEE) can exert effects on various populations of intestinal cells, and even interact with immune cells in the intestinal lamina propria or enter the bloodstream. Evidence suggests that some HEE receptors have immunoregulatory properties. In this work, we hypothesize that the immune system cells may undergo modulation in their differentiation or activation through HEE receptors. Objective: To evaluate the expression of GIPR, GLP-1R, SSTR receptors, and CD26 in macrophage (MØ) polarization and activation of dendritic cells (DC) in response to treatment with sitagliptin. Methods: We utilized bioinformatics analysis to explore the differential expression of HEE receptors in polarized MØ and DCs. MØ culture generation was performed from murine bone marrow cells using 20% of L929-conditioned-medium in RPMI medium for 6 days (M0). M1 was induced by stimulating M0 cells with IFN-γ [10 ng/mL] and LPS [100 ng/mL], while M2 polarization was induced by IL-4 [10 ng/mL] and IL-13 [10 ng/mL] for 24 h. DCs were cultured from murine bone marrow-derived cells with GM-CSF [20 ng/mL] in IMDM medium for 6 days. Activation of DCs was achieved by treating them with LPS [20 ng/mL] (aDC) for 24 h, while DCs untreated were considered immature (iDC). Sitagliptin treatment was performed during the 24 h period of MØ polarization and DC activation. We assessed the frequency of GLP-1R+ and CD26+ (DPP-4) cells in these populations. For MØ cells, we evaluated the frequency of CD86+ and CD206+ cells during polarization, as well as the glucose and lactate concentrations in the cell supernatant. For DCs, we examined the frequency of IA/IE+ (MHC II), CD80+, and CD86+ cells upon activation. Results: In silico analysis revealed higher levels of SSTR 2 and 5 in M1 compared to M2. The expression of GLP-1R and GIPR remained unchanged. In DCs, different phenotypes exhibited variations in the expression of GIPR, HRH1, HTR7, and Nucb2 receptors. Protein expression of GLP-1R was undetectable in both MØ and DCs, as well as CD26 in DCs. The frequency of CD26+ cells was higher in M0 compared to M1 and M2, being more pronounced in M1. In vitro, treatment with sitagliptin increased the frequency of CD206+ cells in M2 but had no effect on DC activation. Conclusion: MØ M1 polarization increases SSTR2 and SSTR5 expression and treatment with sitagliptin modulates polarization in M2, despite the higher frequency of CD26+ cells in M0 and M1.

COMMITTEE MEMBERS:
Presidente - Interno ao Programa - 1640114 - MARCELA SORELLI CARNEIRO RAMOS
Membro Titular - Examinador(a) Externo ao Programa - 2353139 - ELOAH RABELLO SUAREZ
Membro Titular - Examinador(a) Externo à Instituição - MARIANE TAMI AMANO
Membro Suplente - Examinador(a) Interno ao Programa - 1061225 - CRISTINA RIBAS FURSTENAU