B1: Diet as an intervention in autoimmune pre-disease
Background. The increased prevalence of autoimmune diseases has been paralleled by dramatic changes in diet. The causal relationship between diet and autoimmune disease is supported by the clinical improvement in rheumatoid arthritis by dietary restriction (Lancet. 338:899). The molecular basis of the beneficial effects of diet has so far remained rather elusive. In project- related, preliminary work that was conducted within the framework of the RTG1743, we demonstrated that diet overrides genetic lupus susceptibility: Mice on dietary restriction did not develop lupus, whereas almost all mice on Western diet died thereof. We linked this to diet-induced changes in the gut microbiota and RNA expression in immune cells. Specifically, we showed that (i) diet-induced changes in the intestinal micro-/mycobiome precede disease onset, and (ii) expression of certain disease-associated genes, i.e., Tnxb, are controlled by diet (Nat Commun. 10:4097).
Objectives. (i) Explore whether therapeutic dietary restriction at different time points can modulate the manifestation of lupus. (ii) Investigate molecular clues underlying the effects of diet in experimental autoimmune disease.
Work program. We will expose lupus-prone NZM2410/J mice to dietary interventions, which will start (i) before disease onset, (ii) when autoantibodies are detected or (iii) at the initial manifestation of clinical disease. Endpoints include (change of) clinical disease manifestation, detailed immunologic and metabolic phenotyping, as well as defining microbial communities longitudinally. To explore the molecular pathways, we will generate CRISPR/Cas constructs (i.e., of the identified Tnxb) and evaluate the impact on lupus susceptibility in both lupus-prone and lupus-resistant mice fed different diets. Specifically, we will generate transgenic mice with the lupus-protective allele from NZM2410/J mice in different genetic backgrounds, as well as NZM2410/J mice with the "wild-type" non-lupus protective Tnxb variant. These "criss-cross" transgenics will be exposed to dietay interventions and nephritis manifestation will be monitored longitudinally.

- Projects
- 1st Generation
- A: Defining Autoimmune Pre-Disease
- B: Targeting of Autoimmune Pre-Disease
- Associated projects
- Medical doctoral researcher projects
- Concluded projects
- Doctoral researchers
- A1: Exploring the pre-disease phase of autoimmunity in lupus-prone mouse models
- A2: B cell activation in murine lupus
- A3: G protein-coupled receptors orchestrating granulocytes in pemphigoid diseases
- A4: Epitope-dependent autoantibody-mediated skin inflammation in pemphigoid diseases
- A5: Chronic danger signaling as driver of autoimmunity in granulomatosis with polyangiitis
- A6: Combining in-depth immune profiling and multi-omics approaches identifies distinct signatures in the early stage of systemic sclerosis
- A7: CD4+ T cell receptor sequences during progression towards experimental pemphigoid
- A8: The C5aR2 pathway as a novel checkpoint for B cell activation in autoimmunity
- A9: Comprehensive genetic and comorbidity profiling of autoimmune diseases: Integrating UK Biobank, TriNetX and Global Data
- B1: Diet as an intervention in autoimmune pre-disease
- B2: Influence of anti-TNF treatment on B cell responses and the type of IgG Fc glycosylation
- B3: Clinical and experimental investigation of T helper cytokines dysregulation in systemic sclerosis-associated pulmonary arterial hypertension
- Medical doctoral researchers
- Ass. doctoral researchers
- Ass. medical doctoral researchers
- Doctoral researchers
- 2nd Generation
- 1st Generation