The absence of TNF receptor 1 (TNFR1) increases serum serotonin levels and favors the subsequent development of reactive arthritis in mice

FUNES, SAMANTA CELESTE; JUAN EDUARDO SILVA, ; CLAUDIA AGUILERA MERLO; ROBERTO CARLOS DAVICINO; MATÍAS DISTEL; MARÍA ELENA ARCE; JAVIER ELICABE; MARÍA SILVIA DI GENARO

Congreso; Reunión Conjunta SAIC SAI&FAIC SAFIS 2022; 2021

Sociedad Argentina de Inmunología

Serotonin (5-HT) is synthesized mainly in the gut and can regulate innate and adaptive immune functions. Multiple inflammatory factors, such as infections, modulate 5-HT levels in the body. In this sense, antidepressants that modify 5-HT availability also affect inflammatory responses. However, its ability to reduce the severity of autoinflammatory diseases remains to be elucidated. This work aims to study the impact of 5-HT changes in the development of reactive arthritis (ReA). In our study model, mice deficient in TNF receptor 1 (TNFR1 KO) develop ReA as a sequela after infection with Yersinia enterocolitica (Ye). Thus, non-infected TNFR1KO and WT mice were euthanized, and the distal portion of the small intestine was removed, and evaluated by immunofluorescence with an anti-serotonin receptor (SERT) antibody. Serum samples were additionally assayed for 5-HT by HPLC. In addition, WT and TNFR1 KO mice were orally infected with Ye O:3 (1-5x108 colony-forming units). From infection day, fluoxetine (20 mg/kg/day) or water (control) was administrated in the drinking water. The ReA was detected on day 14, and the score was recorded. On day 21, mice were euthanized, and sera samples were taken for 5-HT levels evaluation. Besides, the joints were obtained for histopathological evaluation and cytokines determination by ELISA. Our results indicate that non-infected TNFR1 KO mice have a higher basal serum 5-HT level, although no significant differences are observed in ileum SERT expression. On day 21, fluoxetine-treated mice showed lower serum 5-HT levels and less clinical symptoms severity than controls. Although a significant reduction in proinflammatory cytokines was not detected, the reduction in the clinical score was consistent with less histological damage in the joints. To conclude, increased availability of 5-HT contributes to the development of ReA; however, blockade of SERT with fluoxetine and their consequent reduction in serum 5-HT can attenuate joint damage.