1alpha,25-dihydroxyvitamin D3 induces an autoantigen-specific T-helper 1/T-helper 2 immune shift in NOD mice immunized with GAD65 (p524-543).

Abstract

Prevention of type 1 diabetes in NOD mice by 1,25-dihydroxyvitamin D 3 [1␣,25(OH) 2 D 3 ] is accompanied by a T-helper (Th) 1/Th2 cytokine shift in the pancreas. The aim of this study was to investigate whether this immune shift also occurs outside of the pancreas and whether it is limited to autoantigen-specific immune responses. NOD mice treated with 1␣,25(OH) 2 D 3 (5 µg/kg every 2 days) or control vehicle were immunized with GAD65 (p524-543) or ovalbumin (OVA) in the rear footpads. First, we examined T-cell proliferation and cytokine production (via enzyme-linked immunosorbent assay) of draining lymph node cells in vitro with or without peptide rechallenge. Although no differences in proliferation were measured between control and 1␣,25(OH) 2 D 3 -treated mice after in vitro GAD65 rechallenge, a marked shift in cytokine secretion profile was seen in 1␣,25(OH) 2 D 3 -treated mice: interleukin-4 was increased (37 ± 5 vs. 21 ± 12 pg/ml in controls, P < 0.005), whereas ␥-interferon levels were decreased (6 ± 3 vs. 9 ± 3 ng/ml in controls, P < 0.05). This shift was absent in OVA-primed mice. Second, we measured cytokine profiles by reverse transcriptase-polymerase chain reaction in popliteal lymph nodes at different time points after priming with GAD65 or OVA in vivo. A marked Th1/Th2 shift occurred in 1␣,25(OH) 2 D 3 -treated mice after in vivo priming with GAD65. Again, this shift was absent after OVA immunization. Finally, we measured cytokine profiles after rechallenge with a panel of autoantigens (GAD65, heat shock protein 65, insulin Bchain) and control antigens (OVA, keyhole limpet hemocyanine, myelin proteolipid protein, tetanus toxin) and confirmed the Th1/ Th2 shift in autoantigen-injected mice but not in control antigen-injected mice. In conclusion, the immune deviation induced by 1␣,25(OH) 2 D 3 in NOD mice can also be induced in the peripheral immune system but is limited to pancreatic autoantigens.

1,25-dihydroxyvitamin D3 Modulates Cytokine Production Induced by Candida albicans: Impact of Seasonal Variation of Immune Responses

“…We have shown that 1,25(OH) 2 D 3 has a distinct propensity to skew host response to C. albicans away from a ''proinflammatory'' profile through attenuation of TNF-a, IL-6, IFN-c as well as production of IL-17. Other researchers have reported inhibition of Th1 cytokine production with 1,25(OH) 2 D 3 , although not in the setting of Candida infection and polarization toward a Th2-type response [21][22][23]. In our system using human PBMC stimulated by C. albicans, we also observed an increase in IL-10 production in vitamin D presence.…”

Vitamin D receptor expression by the lung micro-environment is required for maximal induction of lung inflammation

“…Ligand binding through the VDR mediates several biological activities, including regulation of T helper (Th) cell development and Th cytokine profile [8][9][10]. Located on chromosome 12q, genome wide screens have identified the VDR as a candidate gene associated with asthma [11,12].…”

Immunological role of vitamin D at the maternal–fetal interface

“…As a consequence, initial studies of vitamin D and T cells focused on anti-proliferative responses (Nunn et al 1986, Provvedini & Manolagas 1989, Karmali et al 1991. However, it is now clear that vitamin D also influences the phenotype of T cells, in part by promoting a shift from Th1 cytokine profile to Th2 (Lemire et al 1995, Overbergh et al 2000, Boonstra et al 2001. In this way, it has been proposed that vitamin D could limit potential tissue damage associated with excessive Th1 cellular immune responses by switching to a more humoral Th2 phenotype.…”