Microbial-specific T-cell responses in Crohn's Disease

Crohn’s Disease is thought to arise from an exacerbated immune response towards commensal microbiota, resulting in chronic inflammation of the gut. Specific antibodies to bacterial components such as flagellin have been associated with Crohn’s Disease. The role of these antibodies in the pathogenesis of CD remains unclear. Nonetheless, their presence strongly suggests that a commensal-specific T cell response is generated as well.  Indeed, it is generally accepted that T cells, and more specifically CD4+T cells (Th1 and Th17 cells) play a pathogenic role in CD as they heavily infiltrate involved areas of the intestinal mucosa. Nonetheless, the specificity of memory T cells in CD has been poorly investigated to date. In the lab, we are interested in studying commensal specific CD4+T cell responses, as they may contribute to perpetuation of disease. Identification of these cells could represent an attractive and specific target for the treatment of CD.

No antigen

Commensal antigen

Description: Detection of antigen-specific T cell reactivity. Peripheral Blood Mononuclear Cells (PBMCs) from a Crohn’s disease patient after 7 days of culture in the presence of gut microbial antigens. 10X Magnification. Bright field.

 

Funding:

- Instituto de Salud Carlos III: Proyectos Integrados de Excelencia (PIE13/00033); Coordinator: Elías Campo; PI: Azucena Salas

- Boehringer Ingelheim Pharmaceuticals, Inc.; PI: Azucena Salas

Publications:

 

An RORγt Oral Inhibitor Modulates IL-17 Responses in Peripheral Blood and Intestinal Mucosa of Crohn's Disease Patients.

Bassolas-Molina H, Raymond E, Labadia M, Wahle J, Ferrer-Picón E, Panzenbeck M, Zheng J, Harcken C, Hughes R, Turner M, Smith D, Calderón-Gómez E, Esteller M, Carrasco A, Esteve M, Dotti I, Corraliza AM, Masamunt MC, Arajol C, Guardiola J, Ricart E, Nabozny G, Salas A.

Front Immunol. 2018 Oct 22;9:2307

doi: 10.3389/fimmu.2018.02307. eCollection 2018

Commensal-specific CD4+ lymphocytes in Crohn’s disease show a distinct Th17-biased pro-inflammatory profile.

Calderón-Gómez E, Bassolas-Molina H, Mora-Buch R, Dotti I, Planell N, Esteller M, Gallego M, Martí M, Garcia-Martín C, Martínez-Torró C, Ordás I, Singh S, Panés J, Benítez-Ribas D, Salas A.

 

Gastroenterology 2016 Jun 4.

pii: S0016-5085(16)34576-0.

doi: 10.1053/j.gastro.2016.05.050.