TLR4 and rheumatoid arthritis: The specific effects of Vitamin D on inflammation include the following: (A) In RA synovial fluid, Vitamin D attenuates NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), Toll-like receptor 1 (TLR1), and TLR4 expression [22]; (B) Vitamin D encourages the transition of macrophages from proinflammatory M1 to the M2 state through the STAT-1/TREM-1 pathway [23,24,25]; and (C) Vitamin D supplementation ameliorates DAS28 and ESR levels, and thus, an altered Vitamin D metabolism may also contribute to rheumatoid disease severity [7].