BACKGROUND: Obesity promotes a state of low-grade inflammation that exacerbates chronic inflammatory diseases, such as asthma and inflammatory bowel disease. In transplantation, the survival of organs transplanted into obese patients is reduced compared with allografts in lean recipients. However, whether this is due to increased alloimmunity remains to be addressed conclusively. METHODS: We used a mouse model of high-fat diet (HFD)-induced obesity and assessed immune responses to allogeneic stimulation in vitro, allogeneic splenocyte immunization in vivo, and allogeneic heart transplantation. RESULTS: Our results indicate that HFD altered the composition and phenotype of splenic antigen-presenting cells that led to their enhanced capacity to stimulate T cells. Immunization with allogeneic splenocytes in vivo resulted in increased alloreactivity, as determined by IFNγ production. Moreover, cardiac allograft rejection in HFD mice was modestly accelerated compared to aged-matched control animals fed a low-fat diet, correlating with enhanced alloreactive T cell function. CONCLUSIONS: Our results highlight the increased alloresponse triggered by HFD-induced obesity and its negative impact on transplant outcome.
BACKGROUND:Obesity promotes a state of low-grade inflammation that exacerbates chronic inflammatory diseases, such as asthma and inflammatory bowel disease. In transplantation, the survival of organs transplanted into obesepatients is reduced compared with allografts in lean recipients. However, whether this is due to increased alloimmunity remains to be addressed conclusively. METHODS: We used a mouse model of high-fat diet (HFD)-induced obesity and assessed immune responses to allogeneic stimulation in vitro, allogeneic splenocyte immunization in vivo, and allogeneic heart transplantation. RESULTS: Our results indicate that HFD altered the composition and phenotype of splenic antigen-presenting cells that led to their enhanced capacity to stimulate T cells. Immunization with allogeneic splenocytes in vivo resulted in increased alloreactivity, as determined by IFNγ production. Moreover, cardiac allograft rejection in HFD mice was modestly accelerated compared to aged-matched control animals fed a low-fat diet, correlating with enhanced alloreactive T cell function. CONCLUSIONS: Our results highlight the increased alloresponse triggered by HFD-induced obesity and its negative impact on transplant outcome.
Authors: P M M Moraes-Vieira; E J Bassi; R A Larocca; A Castoldi; M Burghos; A P Lepique; F J Quintana; R C Araujo; A S Basso; T B Strom; N O S Câmara Journal: Am J Transplant Date: 2012-09-27 Impact factor: 8.086
Authors: K L Grady; C White-Williams; D Naftel; M R Costanzo; D Pitts; B Rayburn; A VanBakel; B Jaski; R Bourge; J Kirklin Journal: J Heart Lung Transplant Date: 1999-08 Impact factor: 10.247
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Authors: Claudio Mauro; Joanne Smith; Danilo Cucchi; David Coe; Hongmei Fu; Fabrizia Bonacina; Andrea Baragetti; Gaia Cermenati; Donatella Caruso; Nico Mitro; Alberico L Catapano; Enrico Ammirati; Maria P Longhi; Klaus Okkenhaug; Giuseppe D Norata; Federica M Marelli-Berg Journal: Cell Metab Date: 2017-02-09 Impact factor: 27.287