Journal Article

Hobit- and Blimp-1-driven CD4+ tissue-resident memory T cells control chronic intestinal inflammation

Slawik, Monique, Lukassen, Sören, Spocinska, Marta, Neufert, Clemens, Hildner, Kai, Rath, Timo, López-Posadas, Rocío, Zundler, Sebastian, Stark, Regina, Parga-Vidal, Loreto, Becker, Emily, Atreya, Raja, Ekici, Arif B., Wiendl, Maximilian, Atreya, Imke, Neurath, Markus F., Leppkes, Moritz, van Gisbergen, Klaas P. J. M.

2019

Overview

Although tissue-resident memory T cells (T RM cells) have been shown to regulate host protection in infectious disorders, their function in inflammatory bowel disease (IBD) remains to be investigated. Here we characterized T RM cells in human IBD and in experimental models of intestinal inflammation. Pro-inflammatory T RM cells accumulated in the mucosa of patients with IBD, and the presence of CD4 + CD69 + CD103 + T RM cells was predictive of the development of flares. In vivo, functional impairment of T RM cells in mice with double knockout of the T RM -cell-associated transcription factors Hobit and Blimp-1 attenuated disease in several models of colitis, due to impaired cross-talk between the adaptive and innate immune system. Finally, depletion of T RM cells led to a suppression of colitis activity. Together, our data demonstrate a central role for T RM cells in the pathogenesis of chronic intestinal inflammation and suggest that these cells could be targets for future therapeutic approaches in IBD. Tissue-resident memory T cells (T RM cells) have well-described functions in the protective response to infectious agents. Neurath and colleagues demonstrate that intestinal T RM cells can also have key pathogenic roles in inflammatory bowel disease.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 692/699/249/2510/1389 / 692/699/249/2510/1402 / 692/699/249/2510/257 / Animal models / Animals / Biomedical and Life Sciences / Biomedicine / CD103 antigen / CD4 antigen / CD69 antigen / CD8-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - metabolism / Cells, Cultured / Chronic Disease / Colitis / Colitis - genetics / Colitis - immunology / Colitis - metabolism / Colon / Cytokines - genetics / Cytokines - immunology / Cytokines - metabolism / Disease Models, Animal / Gene Expression Profiling / Humans / Immune system / Immunologic Memory - genetics / Immunologic Memory - immunology / Immunological memory / Immunology / Infectious Diseases / Inflammation / Inflammatory bowel disease / Inflammatory bowel diseases / Inflammatory Bowel Diseases - genetics / Inflammatory Bowel Diseases - immunology / Inflammatory Bowel Diseases - metabolism / Innate immunity / Intestine / Lymphocytes / Lymphocytes T / Memory cells / Mice, Inbred C57BL / Mice, Knockout / Mice, Transgenic / Mucosa / Positive Regulatory Domain I-Binding Factor 1 - deficiency / Positive Regulatory Domain I-Binding Factor 1 - genetics / Positive Regulatory Domain I-Binding Factor 1 - immunology / Rodents / Transcription factors / Transcription Factors - deficiency / Transcription Factors - genetics / Transcription Factors - immunology