Arthritis Protection By Estrogens: Driving Th17 Cells To Lymph Nodes But Restricting Their Migration to the Joints?
Annica Andersson and colleagues from the Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden published in Arthritis Research & Therapy a study indicating that the regulation exerted by estrogens, to the Th17 cell traffic and migration, may play an important role in the well established protective role of female hormones in rheumatoid arthritis (RA).
The sexual dimorphism in autoimmune diseases is a well-known but still not fully understood phenomenon. Thus, maladies such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis and autoimmune thyroid diseases have an increased incidence and prevalence in females.
In rheumatoid arthritis, the female-to-male ratio is 3:1, with the peak RA’s incidence in women during menopause, when estrogen levels rapidly drop. Interestingly, estrogen levels are lower in postmenopausal women than in men of corresponding age.
Th17 cells are major pro-inflammatory and pathogenic cells in many autoimmune and inflammatory diseases. In RA, Th17 cell frequency or level in the synovial fluid correlates with disease activity, IL-8 production and inflammation-induced bone loss.
Now, the research group from Gothenburg, Sweden found that in the murine collagen-induced arthritis model, estrogen regulates traffic of Th17 cells during the development of arthritis, by increasing the migration of Th17 in early arthritis to the lymph nodes and decreasing Th17 migration to joints in established arthritis.
As estradiol increased CCR6 expression on lymph nodes’ Th17 cells and the production of CCL20, the authors suggest that the interactions within the CCR6-CCL20 pathway are responsible for the retention of Th17 cells within the lymph nodes. This may explain why the Th17 cell migration to joints is prevented, which contributes to the diminished neutrophils’ recruitment and reduced joint’s inflammation.
Thus, the study may provide new insights into mechanisms driving the sexual dimorphism in rheumatoid arthritis.
Source: Arthritis Research & Therapy2015, 17:32 doi:10.1186/s13075-015-0548-y
Read more: arthritis-research.com
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