N-3 polyunsaturated fatty acids restore Th17 and Treg balance in collagen antibody-induced arthritis

PLoS One. 2018 Mar 15;13(3):e0194331. doi: 10.1371/journal.pone.0194331. eCollection 2018.


N-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory effects and were considered useful for the treatment of rheumatoid arthritis (RA). Recently, several studies suggested that n-3 PUFAs attenuated arthritis in animal model and human, however the mechanism is still unclear. Interleukin 17 (IL-17) is a pro-inflammatory cytokine mainly produced by T helper 17 (Th17) cells which cause tissue inflammation and bone erosion leading to joint destruction. In contrast, regulatory T (Treg) cells down-regulate various immune responses by suppression of naïve T cells. The imbalance between Th17 cells and Tregs cell is important for the pathogenesis of RA. Here, we investigated whether n-3 PUFAs attenuate arthritis in collagen antibody-induced arthritis (CAIA) model. We used fat-1 transgenic mice expressing the Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid desaturase that converts n-6 to n-3 fatty acids, leading to abundant n-3 fatty acids without the need of a dietary n-3 supply. Clinical arthritis score was significantly attenuated in fat-1 mice compared to wild type (WT) mice on day 7 (1.6±1.8, p = 0.012) and day 9 (1.5±1.6, p = 0.003). Ankle thickness also decreased significantly in fat-1 mice compared to WT mice (1.82±0.11, p = 0.008). The pathologic finding showed that inflammatory cell infiltration and bone destruction were reduced in fat-1 mice compared to WT. The expression levels of IL-17 and related cytokines including IL-6 and IL-23 decreased in the spleen and ankle joint tissue of fat-1 mice compared to WT mice. Furthermore, Treg cells were expanded in the spleen of fat-1 mice and Treg cell differentiation was significantly higher in fat-1 mice than in wild type (p = 0.038). These data suggest that n-3 PUFAs could attenuate arthritis through increasing the expression of FoxP3 and the differentiation of Treg, while reducing IL-17 production. Therefore, dietary supplementation of n-3 PUFAs could have a therapeutic potential for the treatment of RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / metabolism*
  • Anti-Inflammatory Agents / therapeutic use
  • Antibodies / immunology
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / metabolism
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Differentiation / drug effects
  • Collagen / antagonists & inhibitors
  • Collagen / immunology
  • Cytokines / metabolism
  • Dietary Supplements
  • Fatty Acid Desaturases / genetics
  • Fatty Acid Desaturases / metabolism
  • Fatty Acids, Omega-3 / metabolism*
  • Fatty Acids, Omega-3 / therapeutic use
  • Fatty Acids, Omega-6 / metabolism
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Spleen / metabolism
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology


  • Anti-Inflammatory Agents
  • Antibodies
  • Caenorhabditis elegans Proteins
  • Cytokines
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • fat-1 protein, C elegans
  • Collagen
  • Fatty Acid Desaturases

Grants and funding

Ji Young Kim was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (MEST) under Grant number: NRF-2013R1A1A2057950 (http://www.nrf.re.kr/nrf_tot_cms/index.jsp). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.