Dissecting the Heterogeneity in T-Cell Mediated Inflammation in IBD

• Published in: Cells (Basel, Switzerland) Switzerland), 2020-01, Vol.9 (1), p.110
• Main Authors: Tindemans, Irma, Joosse, Maria E, Samsom, Janneke N
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Antigens; Bacteria; CD4 antigen; cd4+ t-cell; Cell Differentiation - immunology; Cell Plasticity - immunology; Chemokines; Colon; Cytokines; Genotype & phenotype; Helper cells; Humans; ibd; Immunological memory; Inflammation; Inflammation - immunology; Inflammatory bowel disease; Inflammatory Bowel Diseases - immunology; Intestine; Lamina propria; Large intestine; Ligands; Lymphatic system; Lymphocytes T; Pathogens; Pathophysiology; Patients; Phenotypes; Review; Small intestine; t helper cell; T-Lymphocytes - immunology; Transcription factors; Tumor necrosis factor-TNF
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9010110

Infiltration of the lamina propria by inflammatory CD4 T-cell populations is a key characteristic of chronic intestinal inflammation. Memory-phenotype CD4 T-cell frequencies are increased in inflamed intestinal tissue of IBD patients compared to tissue of healthy controls and are associated with disease flares and a more complicated disease course. Therefore, a tightly controlled balance between regulatory and inflammatory CD4 T-cell populations is crucial to prevent uncontrolled CD4 T-cell responses and subsequent intestinal tissue damage. While at steady state, T-cells display mainly a regulatory phenotype, increased in Th1, Th2, Th9, Th17, and Th17.1 responses, and reduced Treg and Tr1 responses have all been suggested to play a role in IBD pathophysiology. However, it is highly unlikely that all these responses are altered in each individual patient. With the rapidly expanding plethora of therapeutic options to inhibit inflammatory T-cell responses and stimulate regulatory T-cell responses, a crucial need is emerging for a robust set of immunological assays to predict and monitor therapeutic success at an individual level. Consequently, it is crucial to differentiate dominant inflammatory and regulatory CD4 T helper responses in patients and relate these to disease course and therapy response. In this review, we provide an overview of how intestinal CD4 T-cell responses arise, discuss the main phenotypes of CD4 T helper responses, and review how they are implicated in IBD.