1,25‐Dihydroxyvitamin D3 Exerts Opposing Effects to IL‐4 on MHC Class‐II Antigen Expression, Accessory Activity, and Phagocytosis of Human Monocytes

Abstract

To investigate the differentiation and activation of monocytes, the combined effects of 1,25-dihydroxyvitamin D3 (D3) and IL-4 on human blood monocytes were examined with respect to expression of MHC class-II antigens, accessory activity, and phagocytic capacity. IL-4 was reported to upregulate the expression of MHC class-II antigens and accessory activity of monocytes. The experiments described here demonstrate that D3 inhibits the expression of all three subtypes of MHC class-II antigens (HLA-DR, -DP and -DQ) as well as the accessory activity of monocytes, both in a dose- and time-dependent manner. However, D3 enhances the immunoglobulin- and complement-dependent phagocytosis by monocytes in a dose- and time-dependent manner. When monocytes are treated with both IL-4 and D3, the effects of D3 are reverted by IL-4, suggesting that IL-4 induces the development of monocytes into accessory cells, whereas D3 stimulates differentiation of monocytes into classical macrophages. These findings provide further evidence for the contention that, depending on defined stimuli, monocytes may develop either into accessory cells or into classical macrophages.

1-alpha,25-Dihydroxyvitamin D3 (1,25(OH)(2)D(3)) hampers the maturation of fully active immature dendritic cells from monocytes

“…There are no reports on the effects of 1,25(OH) 2 D 3 on IL-10 and IL-12 production by immature DCs, but maturing DCs were affected by the presence of 1,25(OH) 2 D 3 , as re¯ected in decreases in the production of the active IL-12 dimer p75 upon exposure to CD40 ligand (10,11) and an upregulation in IL-10 production (10). This suppressive action of 1,25(OH) 2 D 3 on DC development is in accordance with the numerous reports of a downregulation of MHC Class II expression in mononuclear cells exposed to this hormone (8,9). There are no previous reports indicating whether or not this suppressive action of 1,25(OH) 2 D 3 is re¯ected in the TGF-b production by DCs.…”

“…Data on the effects of 1,25(OH) 2 D 3 on the accessorycell function of monocytes/macrophages demonstrate reduced antigen-presenting capacity, together with reduced major histocompatibility complex (MHC) class II antigen expression (8,9). Dendritic cells (DCs) ± which are highly specialized antigen-presenting accessory cells (APCs) capable of stimulating naõ Ève T cells ± can be generated from monocytes by culture for 1 week under plastic-adherent conditions in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4.…”

Vitamin D3and the immune system: maintaining the balance in health and disease

“…Exposing monocytes and macrophages to 1,25(OH) 2 D 3 improves their chemotactic and phagocytotic capacity, both features that are indispensable for their tumour cell cytotoxicity and microbacterial activity 93 . Monocytes and macrophages are, next to their role as APC in the stimulation of T cellmediated immune responses, key players in mounting innate immune responses against various infectious agents, including bacteria, viruses, fungi and parasites.…”

“…It is, however, important to realise that this study was conducted in mice already having multiple immune abnormalities, comprising a lower sensitivity to AICD in T lymphocytes 92 59 . Exposing macrophages to 1,25(OH) 2 D 3 enhances their chemotactic and phagocytic capacity, which is indispensable for their tumour cell cytotoxicity and microbacterial activity 93 . In contrast, 1,25(OH) 2 D 3 seriously impairs the antigen-presenting and T cell-stimulatory capacities of monocytes and macrophages; surface expression of MHC class II and co-stimulatory molecules, such as CD40, CD80 and CD86, is down regulated when monocytes are exposed to 1,25(OH) 2 D 3 in vitro 93 .…”

“…Exposing macrophages to 1,25(OH) 2 D 3 enhances their chemotactic and phagocytic capacity, which is indispensable for their tumour cell cytotoxicity and microbacterial activity 93 . In contrast, 1,25(OH) 2 D 3 seriously impairs the antigen-presenting and T cell-stimulatory capacities of monocytes and macrophages; surface expression of MHC class II and co-stimulatory molecules, such as CD40, CD80 and CD86, is down regulated when monocytes are exposed to 1,25(OH) 2 D 3 in vitro 93 . Among the APC, dendritic cells play a pivotal role in initiating and regulating T cell responses.…”