T helper cell subsets in arthritis and the benefits of immunomodulation by 1,25(OH)2 vitamin D

Abstract

The prevalence of vitamin D deficiency has been shown to be increased in many of the common arthritides. Importantly, vitamin D has significant immunomodulatory effects in addition to its role in calcium homoeostasis. Both aspects of its function have a major bearing on joint disease whether as part of an inflammatory arthritis or from wear and tear. While the exact mechanisms still require clarification, there is now compelling evidence that the hormonally active 1,25-dihydroxycholecalciferol vitamin D can reduce the activity of the proinflammatory Th1 and Th17 T cell subsets. Additionally, it is stimulatory of enhanced anti-inflammatory Th2 activity at the same time as promoting T regulatory cell activity. These various actions suggest that correcting vitamin D deficiency should be a important part of the management of all patients with joint disease. For the future, vitamin D analogues with enhanced immunomodulatory properties but with reduced ability to increase calcium are being investigated.

25‐Hydroxyvitamin D2/D3 levels and factors associated with systemic inflammation and melanoma survival in the Leeds Melanoma Cohort

“…Low vitamin D levels are associated with higher circulating proinflammatory cytokines in HIV positive patients with increased CD4+ counts in those treated with vitamin D . In rheumatoid diseases there are data to support that vitamin D reduces proinflammatory T‐cell subsets TH 1 and TH 17 …”

“…We use the 20-60 nmol/L category as the baseline as this was the largest group. BMI (kg/m 2 ) was classified using the standard classification system defined by the World Health Organization of underweight (<18.5), normal (18.5-25), overweight (25)(26)(27)(28)(29)(30) and obese (301). 23 Cases were interviewed about whether they had diabetes and about their smoking habits.…”

“…22 Low vitamin D levels are associated with higher circulating proinflammatory cytokines in HIV positive patients 27 with increased CD41 counts in those treated with vitamin D. 28 In rheumatoid diseases there are data to support that vitamin D reduces proinflammatory T-cell subsets TH 1 and TH 17. 29 In the Leeds Melanoma Cohort we collected data on exposures and concurrent illnesses associated with systemic inflammation. We have therefore tested the hypothesis that obesity and diabetes might be associated with increased mortality from melanoma and investigated whether vitamin D levels were statistically independently protective.…”

Vitamin D Deficiency and Rheumatoid Arthritis

“…Even though PG alone did not modify cytokine production, animals that received VitD3+PG association produced significantly lower cytokine levels after specific stimulation. The therapeutic effect of VitD3 is already well documented in experimental arthritis [112,113]; however, our results constitute the first direct in vivo assessment of its tolerogenic potential. Recently, it was demonstrated that the association of VitD3 with myelin oligodendrocyte glycoprotein-derived [93].…”

Can We Translate Vitamin D Immunomodulating Effect on Innate and Adaptive Immunity to Vaccine Response?

“…, IL17 to provide anti-microbial immunity at epithelial and mucosal barriers) [ 31 ] in order to polarize the CD4 + T-cells responses toward a more regulatory Th2 ( i.e. , IL2 which activate humoral-mediated immunity by the production of neutralizing antibodies by B-cells to induce protection against extracellular pathogen) [ 32 ] or Threg phenotypes [ 14 , 33 ]. These two last phenotypes are considered key components of VitD capacity to suppress Th1-driven autoimmunity responses [ 28 , 33 ].…”