ASTROPHYSICS

Bringing black holes into focusChristopher S. Reynolds

Do black holes exist? Observations at the finest resolution so far indicate that only gross deviations in the behaviour of gravity from that predicted by general relativity can invalidate the case that they do.

It is believed that the centre of essentially every galaxy, including our own, plays host to a supermassive black hole. In a small fraction of galaxies, large quantities of gas rain down into these giant black holes, causing the black hole to grow while releasing enough energy within the central few light hours of the galaxy to outshine all of the galaxy’s stars thousands of times over. This is more than a mere cosmic firework show; the energy released as the black hole grows can shape or even shut off the pro cesses by which the galaxy itself forms. In other words, supermassive black holes may well be the safety valve that regulates galaxy formation, preventing galaxies from growing too big too fast. But although they are rapidly becoming a standard part of our model of how galaxies form and evolve, it is important to step back and ask just how strong is the case that these monster black holes actually exist.

On page 78 of this issue, Doeleman et al.1 report new observations of Sagittarius A* (Sgr A*), the enigmatic source of radio waves at the centre of our Galaxy2 that has long been suspected as signposting our very own supermassive black hole. These new data have allowed the authors, for the first time, to detect structure in the radio emissions from Sgr A* on scales as small as 50 million kilometres. The diameter of our Galaxy’s black hole (which has a mass 4 million times that of the Sun) is expected to be approximately 12 million to

24 million kilometres. But the strong bending of light rays within the gravitational field of the black hole will double the apparent size of the event horizon, the boundary of the area around the black hole from which nothing, not even light, can escape. Thus Doeleman and colleagues’ observations have finally brought us to the threshold of imaging horizon-scale structures — a holy grail of radio astronomy.

With the new data, the authors have attained a resolution of about 40 microarcseconds (about one-hundred millionth of a degree), five times better than the best previous measure-ment3. This advance has been made possible by extending the technique of very long baseline interferometry (VLBI) to shorter radio wave-lengths — indeed, into the microwave region of the electromagnetic spectrum. In VLBI, data from radio telescopes spread across the globe are combined to produce vastly superior image resolution than can be achieved by any one tele-scope; but this process requires keeping track of the precise phase of the incoming waves. This technological feat becomes increasingly challenging as the wavelength of the waves is decreased in the search for superior resolving power. The observation reported by Doeleman et al.1, made with telescopes in Arizona, Cali-fornia and Hawaii, is one of the first to exploit VLBI with 1.3-mm waves.

Black holes are truly bizarre objects. Ein-stein’s theory of general relativity tells us that

they are objects in which gravity has run amok, cutting off a region of space (inside the event horizon) from the outside Universe. Inside the event horizon, theory predicts the existence of regions in which densities and temperatures climb to such extreme values that all currently understood laws of physics break down. These new results1 put us a step closer to confirming that nature really is this anarchistic. Assuming that the central object must be smaller than the surrounding ‘cloud’ of radio-emitting gas that we see, the case for a black hole looks compel-ling. Even a 4-million-solar-mass boson star, an exotic hypothetical object sometimes discussed as an alternative to black holes4, will be much larger in extent than the 50-million-kilometre limit implied by Doeleman and colleagues’ data. Given these data, only gross deviations in the behaviour of gravity itself from the behaviour predicted by general relativity can invalidate the case for black holes.

Efforts to improve the sensitivity and imaging ability of millimetre-wavelength VLBI promise further dramatic advances in our understand-ing of Sgr A*. For example, future studies will reveal effects related to the spin of the black hole. Although still the subject of intense research, the complex gas flows close to a black hole can be strongly affected by the tornado-like motion of space-time close to a spinning black hole5, as can the appearance of the ‘shadow’ of the event horizon6. Characterizing these phenomena will

The Galactic Centre. This radio image, obtained with the Very Large Array of telescopes, shows the central region

of our Milky Way galaxy. The bright object at the centre is Sagittarius A*, the enigmatic source of radio waves that has

long been suspected of harbouring a supermassive black hole.

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allow us to determine the spin rate of the black hole, offering a window into its long cosmic his-tory. Did it grow through the successive mergers of smaller black holes as galaxies came crashing together? Or did it grow through the accretion of gas and, if so, did it snack on gas hundreds of times7 or feast just once or twice? The spin of the black hole encodes, albeit crudely, this history and may be one of our best handles for understanding the evolution of this, and other, supermassive black holes8.

We have entered a new era, one in which we can now directly image structure at the event horizon of a black hole. As the VLBI array capable of millimetre resolution is expanded and its sensitivity increased, the distorted

world at the edge of the black hole will literally come into focus. ■ Christopher S. Reynolds is in the Department of Astronomy, University of Maryland, College Park, Maryland 20742, USA.e-mail: chris@astro.umd.edu

1. Doeleman, S. S. et al. Nature 455, 78–80 (2008).2. Balick, B. & Brown, R. L. Astrophys. J. 194, 265–270 (1974).3. Shen, Z. Q., Lo, K. Y., Liang, M.-C., Ho, P. T. P. & Zhao, J.-H.

Nature 438, 62–64 (2005).4. Torres, D. F., Capozziello, S. & Lambiase, G. Phys. Rev. D 62,

104012 (2000).5. Krolik, J. H., Hawley, J. F. & Hirose, S. Astrophys. J. 622,

1008–1023 (2005).6. Reynolds, C. S. Nature 438, 32–33 (2005).7. King, A. R. & Pringle, J. E. Mon. Not. R. Astron. Soc. 377,

L25–L28 (2007).8. Volonteri, M. et al. Astrophys. J. 620, 69–77 (2005).

IMMUNOLOGY

Oxysterols hold T cells in check Christopher K. Glass and Kaoru Saijo

The oxysterol-dependent gene transcription factor LXRβ restricts premature expansion of T cells by limiting cellular cholesterol levels. This pathway might be a pharmacological target for regulating immune responses.

Adaptive immune responses depend on the activation and expansion of specific subsets of white blood cells such as T cells in response to antigens. Although it has long been appre-ciated1,2 that such proliferative responses are linked to the uptake and de novo synthesis of cholesterol for membrane formation, whether cholesterol-efflux pathways can limit cell divi-sion has not been considered. Reporting in Cell, Bensinger et al.3 provide evidence that cholesterol efflux is indeed used to inhibit the proliferation of resting T cells — T cells that have not yet encountered an antigen.

Intracellular cholesterol levels are tightly regulated by two complementary pathways that are mediated by the gene transcription factors SREBP and LXR. The SREBP-depend-ent pathway induces the expression of proteins that are required for cholesterol biosynthesis and uptake, such as HMG CoA reductase and the LDL receptor, thereby increasing cellular cholesterol levels4. This pathway is regulated by feedback inhibition, but it cannot eliminate excess cholesterol once this lipid has accu-mulated. That task is in part accomplished by choles terol-efflux pathways that are regu-lated by LXRα and LXRβ — members of the nuclear-receptor superfamily. Oxidized choles-terol derivatives (oxysterols) activate LXRs5, which then control the transcription of genes that have diverse roles in cholesterol homeo-stasis and innate immunity6. For example, in many cell types LXRs promote a reduction in cellular cholesterol levels by inducing the expression of the ABCA1 and ABCG1 trans-porters, which mediate cholesterol efflux from the cell to extracellular acceptors.

Bensinger et al.3 find that mice lacking both LXRα and LXRβ develop enlarged spleens and lymph nodes owing to increased numbers of immune B cells and T cells. T cells express only LXRβ, and its loss seems to be responsi-ble for the increased numbers of these cells.

The authors find that LXRβ-deficient T cells exhibit higher rates of proliferation in response to antigens, both in vitro and in vivo, and that in mutant mice lacking mature T cells in their lymphoid organs, these cells more efficiently repopulate the lymphoid organs than do normal T cells.

Bensinger et al. find that cholesterol levels in dividing T cells are determined by the reciprocal regulation of the LXR and SREBP transcriptional programs. They show that activation of T cells by antigens results in increased activity of the SREBP pathway and simultaneously reduced LXR activity. These changes alter the balance of cholesterol homeo stasis to allow membrane formation and cellular proliferation (Fig. 1).

Intriguingly, inhibition of LXR signal-ling seems to be — at least in part — due to the induction of the oxysterol-metabolizing enzyme SULT2B1, which inactivates these natural LXR ligands by adding sulphate groups to them7. Synthetic LXR ligands also potently inhibit the proliferative responses of normal T cells to antigens, overriding the effect of eliminating natural LXR ligands3. This effect is lost in T cells lacking the ABCG1 transporter, indicating a direct link between the antiprolif-erative activities of LXR ligands and cholesterol efflux. So in the absence of antigens, LXR-mediated limitation of cholesterol availability seems to serve as a checkpoint to restrict T-cell proliferation.

Several questions emerge from this study3. Of immediate interest is determining the extent to which these observations apply to

Figure 1 | Response of T cells to a shift in cholesterol balance. a, Bensinger et al.3 find that, in resting T cells, oxysterols activate the transcription factor LXRβ, which in turn leads to increased expression of the ABCG1 transporter for cholesterol transfer out of the cell. In these cells, the activity of the SREBP pathway, which favours de novo cholesterol synthesis and cholesterol uptake, is also low. Consequently, there is a shortage of sterols for membrane biogenesis, which is required for effective proliferative responses. b, Antigenic challenge activates T cells, resulting in upregulation of the SREBP pathway. By increasing the expression of genes encoding HMG CoA reductase and the LDL receptor, this enhances cholesterol uptake and synthesis. Moreover, increased activity of the oxysterol-metabolizing enzyme SULT2B1 and the ABCC1 transporter eliminates oxysterol ligands of LXRβ, leading to reduced activity of cholesterol-efflux pathways. Internalized and newly synthesized cholesterol can now be used for membrane biogenesis, leading to cell proliferation.

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a Resting T cell b Activated T cell

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NATURE|Vol 455|4 September 2008NEWS & VIEWS