Transition from an autoimmune-prone state to fatal autoimmune disease in CCR7 and RORγt double-deficient mice is dependent on gut microbiota
| Autor: | Uta E. Höpken, Katharina Wichner, Markus M. Heimesaat, Stefan Bereswill, Susann Winter, André Fischer, Solveig Tetzlaff, Armin Rehm, Martin Lipp |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
CD4-Positive T-Lymphocytes
Receptors CCR7 T cell Immunology Autoimmunity C-C chemokine receptor type 7 Inflammation Biology Lymphocyte Activation medicine.disease_cause Autoimmune Diseases Mice Chemokine receptor RAR-related orphan receptor gamma Lymphocyte homeostasis Leukocytes medicine Animals Immunology and Allergy Intestinal Mucosa Autoantibodies Mice Knockout Autoimmune disease Chimera Colistin Microbiota Cell Differentiation Nuclear Receptor Subfamily 1 Group F Member 3 medicine.disease Anti-Bacterial Agents Mice Inbred C57BL medicine.anatomical_structure Streptomycin Ampicillin medicine.symptom |
| Zdroj: | Journal of Autoimmunity. 47:58-72 |
| ISSN: | 0896-8411 |
| DOI: | 10.1016/j.jaut.2013.08.007 |
| Popis: | Autoimmunity is associated with a strong genetic component, but onset and persistence of clinically apparent autoimmune diseases often require an additional environmental trigger. The balance between immunity and tolerance is regulated by numerous molecular factors including nuclear hormone and homeostatic chemokine receptors. The nuclear hormone receptor ROR{gamma}t and the chemokine receptor CCR7 are both essentially involved in functional lymphoid organogenesis and maintenance of lymphocyte homeostasis. Lack of one or the other impairs thymic T cell development and alters T cell homeostasis. Mice deficient for both, Ccr7-/-Ror{gamma}t-/-, succumbed early to acute destructive inflammation, characterized by massive recruitment of inflammatory leukocytes, pro-inflammatory cytokine and autoantibody production, and wasting disease. Antibiotic-treatment of mice before disease onset reduced the overall gut microflora and abrogated the development of fatal mucosal inflammation. Hence, commensal bacteria and a confined tissue-specific inflammatory milieu serve as complementary trigger to initiate the lethal pathophysiologic process in Ccr7-/-Ror{gamma}t-/- mice. |
| Databáze: | OpenAIRE |
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