RESUMO
Regulatory T cells (Tregs) facilitate primary and metastatic tumour growth through the suppression of anti-tumour immunity. Emerging evidence suggests a distinct role for Tregs in mediating tissue repair and barrier integrity in the lungs by IL-33 mediated production of the growth factor amphiregulin (AREG). Dependent on the type of cancer and local microenvironment, AREG may induce tumour cell proliferation, invasion, migration or resistance to apoptosis by signaling through the epidermal growth factor receptor (EGFR). We have found that IL-33 is dramatically increased in and around metastatic tumour foci in the lungs of mice bearing orthotopic murine mammary tumours. We observed that Tregs express significantly more of the IL-33 receptor, ST2, relative to conventional T cells, that ST2+ Tregs accumulate in the lungs of metastatic tumour-bearing mice, and that ST2+ Tregs produce significantly more AREG than ST2- Tregs. The intranasal administration of recombinant IL-33 increased the proportion of AREG producing ST2+ Tregs and enhanced the level of phosphorylated EGFR in the metastatic lungs. While recombinant AREG did not impact mammary tumour cell proliferation in vitro despite inducing a dose-dependent increase in phosphorylated EGFR, intranasal administration of AREG resulted in a ten-fold increase in pulmonary metastatic tumour burden in vivo. Further, the intranasal administration of recombinant IL-33 significantly increased metastatic tumour burden in the lungs in an amphiregulin-dependent manner. These data identify ST2+ Tregs as a microenvironmental source of AREG in the lungs of mice with orthotopic metastatic mammary tumours and highlight an important role for AREG in promoting metastatic tumour growth in the lungs.
RESUMO
The spin-dependent momentum density of Gd(7)Pd(3) was probed by the magnetic Compton scattering technique with elliptically polarized synchrotron radiation. A contribution to the spin moment from Pd 4d electrons was observed, at 2 and 280 K, alongside a large Gd 4f moment and a smaller Gd 5d moment. The total spin moment, at 2 K, was determined as 50.8 ± 0.7 µ(B) (f.u.)(-1). The Gd 4f contribution to the spin moment was determined as 43.4 ± 1.8 µ(B) (f.u.)(-1), the Gd 5d moment as 4.4 ± 0.7 µ(B) (f.u.)(-1) and the Pd 4d spin moment contribution as 2.9 ± 1.1 µ(B) (f.u.)(-1), where f.u. represents a formula unit. At 280 K the total spin moment was 27.3 ± 0.9 µ(B) (f.u.)(-1) with individual contributions determined as a Gd 4f spin moment of 23.8 ± 1.1 µ(B) (f.u.)(-1), a Gd 5d contribution of 2.2 ± 0.5 µ(B) (f.u.)(-1) and a Pd 5d spin moment of 1.2 ± 0.6 µ(B) (f.u.)(-1).
RESUMO
We have performed a muon spin rotation study on polycrystalline samples of electron-doped layered manganites, La2-2xSr1+2xMn2O7 (0.4< or =x<1), in order to investigate the local magnetic structure and spin dynamics. Our results provide evidence for phase separation into A-type antiferromagnetic and charge-ordered phases for x=0.52 and spin freezing at low temperatures (T<100 K) for 0.52< or =x<0.75. A new phase diagram which includes this spin-freezing region is proposed.
RESUMO
It is shown by magnetometry and microSR spectroscopy that short-range magnetic interactions between the Mn cations in the nonmetallic K(2)NiF(4)-like phase La(0.8)Sr(1.2)Mn(0.6)Rh(0.4)O(4) become significant below approximately 200 K. Negative magnetoresistance (rho/rho(0) approximately 0.5 in 14 T at 108 K) is apparent below this temperature. Neutron diffraction has shown that an applied magnetic field of 5 T is sufficient to induce saturated (3.38(7)mu(B) per Mn) long-range ferromagnetic ordering of the atomic moments at 2 K, and that the induced ordering persists up to a temperature of 50 K in 5 T. Spin glass behavior is observed below 20 K in the absence of an applied field. The induced magnetic ordering is attributed to the subtle changes in band structure brought about by the external field, and to the controlling influence of Rh(3+) over the relative strength of competing magnetic exchange interactions.