1,25‐dihydroxyvitamin D₃ enhances the ability of transferred CD4⁺ CD25⁺ cells to modulate T helper type 2‐driven asthmatic responses

Abstract

Summary The severity of allergic diseases may be modified by vitamin D. However, the immune pathways modulated by the active form of vitamin D, 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3], are yet to be fully elucidated. In this study, naturally occurring CD4+ CD25+ cells from the skin‐draining lymph nodes (SDLN) of mice treated with topical 1,25(OH)2D3 had an increased ability to suppress T helper type 2 (Th2) ‐skewed immune responses. CD4+ CD25+ cells transferred from mice treated with topical 1,25(OH)2D3 into ovalbumin (OVA) ‐sensitized mice challenged intranasally with OVA 18 hr later, significantly suppressed the capacity of airway‐draining lymph node (ADLN) cells to proliferate and secrete cytokines in response to further OVA stimulation ex vivo. The CD4+ CD25+ cells from 1,25(OH)2D3‐treated mice also reduced airway hyperresponsiveness and the proportions of neutrophils and eosinophils in bronchoalveolar lavage fluid (BALF). To test the effect of 1,25(OH)2D3 on cells able to respond to a specific antigen, CD4+ CD25+ cells were purified from the SDLN of OVA‐T‐cell receptor (TCR) transgenic mice treated 4 days earlier with topical 1,25(OH)2D3. CD4+ CD25+ cells from OVA‐TCR mice treated with 1,25(OH)2D3 were able to alter BALF cell content and suppress ADLN responses to a similar degree to those cells from non‐transgenic mice, suggesting that the effect of 1,25(OH)2D3 was not related to TCR signalling. In summary, topical 1,25(OH)2D3 increased the regulatory capacity of CD4+ CD25+ cells from the SDLN to suppress Th2‐mediated allergic airway disease. This work highlights how local 1,25(OH)2D3 production by lung epithelial cells may modulate the suppressive activity of local regulatory T cells.

Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study

“…[13,33]. Both induction [10,34] and activation of regulatory T-cells [12] by 1,25-dihydroxyvitamin D3 have been reported and may explain the correlations observed, possibly indirectly via effects on dendritic cells. The profile of PBMC responses to the TLR4 and TLR3 ligands LPS and poly(I:C), respectively, suggest that in subjects with increased vitamin D levels, there was reduced production of pro-inflammatory TNF, which was balanced by increased production of the regulatory cytokine IL-10.…”

“…Furthermore, vitamin D has been used as a therapy to treat glucocorticoid resistance in some asthmatic patients [9,10], and an association has recently been reported in asthmatic children between serum vitamin D levels and increased glucocorticoid use [5]. Data from rodent models suggest that vitamin D can control sensitisation to allergens by both regulation of dendritic cell development [11] and induction of interleukin (IL)-10-producing CD4+ CD25+ regulatory T-cells [10,12].…”

1,25-Dihydroxyvitamin D3 inhibits proliferation but not the suppressive function of regulatory T cells in the absence of antigen-presenting cells

“…19,20 24 and their ability to suppress T helper type 2 (Th2) activity. 25 However, there is limited information on the direct effects of 1,25(OH) 2 D 3 on human naturally occurring Treg cells. In patients with multiple sclerosis, there is controversy on how serum 25(OH)D 3 levels correlate with the peripheral nTreg cell pool 26,27 though it seems to be implicated in the enhancement of Treg cell suppressive function.…”

Vitamin D with asthma and COPD: not a false hope? A systematic review and meta-analysis

“…In recent years, there has been growing evidence to suggest that vitamin D plays an important role in inflammation (Zasloff, 2006). Vitamin D can suppress Th2-mediated allergic airway disease and may modulate the suppressive activity of local regulatory cells (Gorman et al, 2010), and vitamin D also plays a key role in the regulation of immune function (Hewison, 2012;Ooi et al, 2012).…”