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Front. Immunol. | doi: 10.3389/fimmu.2018.00400

The dynamics of IL-10-afforded protection during DSS-induced colitis

 Ana Cardoso1, 2, 3, 4, 5, 6, Antonio Gil Castro2, 6, Ana Catarina Martins3, 4, Guilhermina Carriche3, 4, Valentine Murigneux1, Isabel Castro2, 6, Ana Cumano1, 5, 7,  Paulo Vieira1, 5, 7* and  Margarida Saraiva3, 4*
  • 1Immunology, Institut Pasteur, France
  • 2Instituto de Pesquisa em Ciências da Vida e da Saúde (ICVS), Portugal
  • 3i3S, Instituto de Investigação e Inovação em Saúde, Portugal
  • 4Instituto de Biologia Molecular e Celular (IBMC), Portugal
  • 5Institut National de la Santé et de la Recherche Médicale (INSERM), France
  • 6ICVS/3B's, Portugal
  • 7Université Paris Diderot, France

Inflammatory bowel disease encompasses a group of chronic-inflammatory conditions of the colon and small intestine. These conditions are characterized by exacerbated inflammation of the organ that greatly affects the quality of life of patients. Molecular mechanisms counteracting this hyper-inflammatory status of the gut offer strategies for therapeutic intervention. Among these regulatory molecules is the anti-inflammatory cytokine interleukin (IL)-10, as shown in mice and humans. Indeed, IL-10 signalling, particularly in macrophages, is essential for intestinal homeostasis. We sought to investigate the temporal profile of IL-10 mediated protection during chemically-induced colitis and which were the underlying mechanisms. Using a novel mouse model of inducible IL-10 over-expression (pMT-10), described here, we show that mice pre-conditioned with IL-10 for 8 days before dextran sulfate sodium (DSS) administration developed a milder colitic phenotype. In IL-10 induced colitic mice, Ly6C cells isolated from the lamina propria showed a decreased inflammatory profile. Because our mouse model leads to transcription of the IL-10 transgene in the bone marrow and elevated seric IL-10 concentration, we investigated whether IL-10 could imprint immune cells in a long-lasting way, thus conferring sustained protection to colitis. We show that this was not the case, as IL-10-afforded protection was only observed if IL-10 induction immediately preceded DSS-mediated colitis. Thus, despite the protection afforded by IL-10 in colitis, novel strategies are required, specifically to achieve long-lasting protection.

Keywords: IL-10, Macrophages, Inflammation, Colitis, therapy

Received: 11 Aug 2017; Accepted: 13 Feb 2018.

Edited by:

Massimo Gadina, National Institute of Arthritis and Musculoskeletal and Skin Diseases, United States

Reviewed by:

CINZIA FIONDA, Sapienza Università di Roma, Italy
Robson Coutinho-Silva, Universidade Federal do Rio de Janeiro, Brazil  

Copyright: © 2018 Cardoso, Gil Castro, Martins, Carriche, Murigneux, Castro, Cumano, Vieira and Saraiva. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Paulo Vieira, Institut Pasteur, Immunology, 25, Rue du Dr Roux, Paris, 75015, France, pvieira@pasteur.fr
Dr. Margarida Saraiva, i3S, Instituto de Investigação e Inovação em Saúde, Rua Alfredo Allen, 208, Porto, Portugal, margarida.saraiva@ibmc.up.pt