The role of obesity-related intestinal microbiota in experimental allogeneic skin transplantation

• Grant number: 17/03248-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2017
• End date: July 16, 2019
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Fernanda Fernandes Terra
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 18/06152-0 - The role of obesity-related changes in the intestinal microbiota in skin graft rejection, BE.EP.MS

Abstract

Despite intense research, graft rejection persists as one of the major complications for end-stage chronic renal patients under replacement therapy. Although advancements in surgical techniques and the development of new immunosuppressive drugs have promoted a relative decrease in the incidence and severity of acute rejection, long-term graft survival is still limited due to chronic rejection and chronic dysfunction. Thus, it is mandatory to understand underlying important factors that could contribute to transplant rejection, focusing in interventions to prolong graft and patient survivals. Acute rejection is mainly caused by allogeneic T cell responses as a consequence of the recognition of donor antigens as non-self by recipient T cells. In this context, many groups have highlighted the intestinal microbiota as a key modulator of immune system and alloimmune responses. Previous data obtained in our lab suggest obesity has a deleterious role in skin transplant rejection. Furthermore, increasing evidences indicate that obesity is also directly related to intestinal dysbiosis, promoting significant changes in indigenous microbiota. Hence, we postulated that obesity-related microbiota is an important mechanism in the aggravation of allograft rejection. Therefore, our aim is to distinguish the role of intestinal dysbiosis and obesity in allograft rejection. This will be done associating specific obesity-related enterotypes to rejection evolution using microbioma analysis, cell activation and immunophenotyping assays in experimental models of skin transplantation, microbiota transfer and probiotics treatment, in obese and lean mice. This study should elucidate the role of obesity and its related gut microbiota in allogeneic transplant rejection and potentially indicate specific enterotypes associated with rejection. Potentially, this study can identify new markers of rejection progression and indicate therapeutic measures to reduce transplant rejection rates.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

TERRA, Fernanda Fernandes. The role of obesity in experimental skin transplant rejection. 2019. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.