Astrocytes as antigen‐presenting cells: expression of IL‐12/IL‐23

Abstract

Interleukin-12 (IL-12, p70) a heterodimeric cytokine of p40 and p35 subunits, important for Th1-type immune responses, has been attributed a prominent role in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Recently, the related heterodimeric cytokine, IL-23, composed of the same p40 subunit as IL-12 and a unique p19 subunit, was shown to be involved in Th1 responses and EAE. We investigated whether astrocytes and microglia, CNS cells with antigen-presenting cell (APC) function can present antigen to myelin basic protein (MBP)-reactive T cells, and whether this presentation is blocked with antibodies against IL-12/IL-23p40. Interferon (IFN)-ctreated APC induced proliferation of MBP-reactive T cells. Anti-IL-12/IL-23p40 antibodies blocked this proliferation.These results support and extend our previous observation that astrocytes and microglia produce IL-12/IL-23p40. Moreover, we show that stimulated astrocytes and microglia produce biologically active IL-12p70. Because IL-12 and IL-23 share p40, we wanted to determine whether astrocytes also express IL-12p35 and IL-23p19, as microglia were already shown to express them. Astrocytes expressed IL-12p35 mRNA constitutively, and IL-23 p19 after stimulation. Thus, astrocytes, under inflammatory conditions, express all subunits of IL-12/IL-23. Their ability to present antigen to encephalitogenic T cells can be blocked by neutralizing anti-IL-12/IL-23p40 antibodies.

Peroxisome Proliferator-Activated Receptor-γ Agonists Suppress the Production of IL-12 Family Cytokines by Activated Glia

“…Some studies indicated that these cells express IL12p40, but not the p70 holoprotein (26). Other studies indicated that astrocytes are capable of producing both IL-12p40 and IL12p70 (27). The present studies indicate that astrocytes constitutively express little or no IL-12p40 (Fig.…”

Astrocytes in the tempest of multiple sclerosis

“…Furthermore, astrocytic iNOS has been demonstrated in MS lesions, and it is recognized as an important pathogenic feature of MS [82]. [57,61,81,[83][84][85][86][87]. Thus, astrocytes could be involved in the complexity of cytokine functions in MS pathogenesis [88].…”

BMP signaling through BMPRIA in astrocytes is essential for proper cerebral angiogenesis and formation of the blood–brain-barrier

“…Angiogenesis is regulated by multiple positive-and negative-regulatory factors, including vascular endothelial growth factor (VEGF), angiopoitins, interferons (alpha/beta/gamma), IL-12, tissue inhibitory metalloproteinase (TIMP)-3 and transforming growth factor-beta 1 (Campbell et al, 1999;Rivieccio et al, 2005;Zeinstra et al, 2006;Constantinescu et al, 2005;Muir et al, 2002;Dhandapani, 2005;Carmeliet, 2000;Petersen et al, 2005;Sidky and Borden, 1987;Raza and Cornelius, 2000;Dhandapani et al, 2005Dhandapani et al, , 2007. VEGF, a prototypical angiogenic growth factor, regulates cell proliferation, vascular permeability, chemotaxis, and survival of ECs and vasculogenesis and angiogenesis in the developing embryo (Ferrara et al, 2003).…”