PMID- 34925335 OWN - NLM STAT- MEDLINE DCOM- 20220218 LR - 20240226 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - Low-Salt Diet Attenuates B-Cell- and Myeloid-Cell-Driven Experimental Arthritides by Affecting Innate as Well as Adaptive Immune Mechanisms. PG - 765741 LID - 10.3389/fimmu.2021.765741 [doi] LID - 765741 AB - A link between high sodium chloride (salt) intake and the development of autoimmune diseases was previously reported. These earlier studies demonstrated exacerbation of experimental autoimmune encephalomyelitis and colitis by excess salt intake associated with Th17- and macrophage-mediated mechanisms. Little is known about the impact of dietary salt intake on experimental arthritides. Here, we investigated if salt restriction can exert beneficial effects on collagen-induced arthritis (CIA) and K/BxN serum transfer-induced arthritis (STIA). CIA depends on both adaptive and innate immunity, while STIA predominantly mimics the innate immune cell-driven effector phase of arthritis. In both models, low salt (LS) diet significantly decreased arthritis severity compared to regular salt (RS) and high salt (HS) diet. We did not observe an aggravation of arthritis with HS diet compared to RS diet. Remarkably, in STIA, LS diet was as effective as IL-1 receptor blocking treatment. Complement-fixing anti-CII IgG2a antibodies are associated with inflammatory cell infiltration and cartilage destruction. LS diet reduced anti-CII IgG2a levels in CIA and decreased the anti-CII IgG2a/IgG1 ratios pointing toward a more Th2-like response. Significantly less inflammatory joint infiltrates and cartilage breakdown associated with reduced protein concentrations of IL-1 beta (CIA and STIA), IL-17 (CIA), and the monocyte chemoattractant protein-1 (MCP-1) (CIA) were detected in mice receiving LS diet compared to HS diet. However, we did not find a reduced IL-17A expression in CD4(+) T cells upon salt restriction in CIA. Analysis of mRNA transcripts and immunoblots revealed a link between LS diet and inhibition of the p38 MAPK (mitogen-activated protein kinase)/NFAT5 (nuclear factor of activated T-cells 5) signaling axis in STIA. Further experiments indicated a decreased leukodiapedesis under LS conditions. In conclusion, dietary salt restriction ameliorates CIA and STIA, indicating a beneficial role of LS diet during both the immunization and effector phase of immune-mediated arthritides by predominantly modulating the humoral immunity and the activation status of myeloid lineage cells. Hence, salt restriction might represent a supportive dietary intervention not only to reduce cardiovascular risk, but also to improve human inflammatory joint diseases like rheumatoid arthritis. CI - Copyright (c) 2021 Sehnert, Pohle, Heuberger, Rzepka, Seidl, Nimmerjahn, Chevalier, Titze and Voll. FAU - Sehnert, Bettina AU - Sehnert B AD - Department of Rheumatology and Clinical Immunology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. FAU - Pohle, Sandy AU - Pohle S AD - Department of Medicine 3, Friedrich-Alexander-University of Erlangen-Nuremberg, Universitatsklinikum Erlangen, Erlangen, Germany. FAU - Heuberger, Cornelia AU - Heuberger C AD - Department of Rheumatology and Clinical Immunology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. FAU - Rzepka, Rita AU - Rzepka R AD - Department of Rheumatology and Clinical Immunology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. FAU - Seidl, Maximilian AU - Seidl M AD - Institute for Surgical Pathology, Department of Pathology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. AD - Institute of Pathology, Heinrich-Heine University and University Hospital of Dusseldorf, Dusseldorf, Germany. FAU - Nimmerjahn, Falk AU - Nimmerjahn F AD - Institute of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erlangen, Germany. FAU - Chevalier, Nina AU - Chevalier N AD - Department of Rheumatology and Clinical Immunology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. FAU - Titze, Jens AU - Titze J AD - Interdisciplinary Center for Clinical Research and Department of Nephrology and Hypertension, Nikolaus-Fiebiger Center for Molecular Medicine, Friedrich-Alexander-University, Erlangen, Germany. AD - Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore, Singapore. FAU - Voll, Reinhard E AU - Voll RE AD - Department of Rheumatology and Clinical Immunology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. AD - Center for Chronic Immunodeficiency (CCI) Freiburg, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211203 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Cytokines) RN - 0 (E-Selectin) RN - 0 (Immunoglobulin G) RN - 0 (Receptors, Interleukin-1) SB - IM MH - Adaptive Immunity MH - Animals MH - *Arthritis, Experimental/blood/genetics/immunology/pathology MH - B-Lymphocytes/immunology MH - Cytokines/genetics/immunology MH - *Diet, Sodium-Restricted MH - E-Selectin/immunology MH - Endothelial Cells/immunology MH - Foot Joints/immunology/pathology MH - Immunity, Innate MH - Immunoglobulin G/blood MH - Mice, Inbred C57BL MH - Mice, Inbred DBA MH - Monocytes/immunology MH - Myeloid Progenitor Cells/immunology MH - Receptors, Interleukin-1/immunology MH - Mice PMC - PMC8678127 OTO - NOTNLM OT - collagen-induced arthritis OT - cytokines OT - diet OT - serum transfer-induced arthritis OT - sodium chloride COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/12/21 06:00 MHDA- 2022/02/19 06:00 PMCR- 2021/01/01 CRDT- 2021/12/20 06:06 PHST- 2021/08/27 00:00 [received] PHST- 2021/11/09 00:00 [accepted] PHST- 2021/12/20 06:06 [entrez] PHST- 2021/12/21 06:00 [pubmed] PHST- 2022/02/19 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.765741 [doi] PST - epublish SO - Front Immunol. 2021 Dec 3;12:765741. doi: 10.3389/fimmu.2021.765741. eCollection 2021.