23 research outputs found
Migration of stem-like CD8 T cells between tissue microenvironments underpins successful anti-tumour immune responses
Salicylic acid receptors activate jasmonic acid signalling through a non-canonical pathway to promote effector-triggered immunity.
It is an apparent conundrum how plants evolved effector-triggered immunity (ETI), involving programmed cell death (PCD), as a major defence mechanism against biotrophic pathogens, because ETI-associated PCD could leave them vulnerable to necrotrophic pathogens that thrive on dead host cells. Interestingly, during ETI, the normally antagonistic defence hormones, salicylic acid (SA) and jasmonic acid (JA) associated with defence against biotrophs and necrotrophs respectively, both accumulate to high levels. In this study, we made the surprising finding that JA is a positive regulator of RPS2-mediated ETI. Early induction of JA-responsive genes and de novo JA synthesis following SA accumulation is activated through the SA receptors NPR3 and NPR4, instead of the JA receptor COI1. We provide evidence that NPR3 and NPR4 may mediate this effect by promoting degradation of the JA transcriptional repressor JAZs. This unique interplay between SA and JA offers a possible explanation of how plants can mount defence against a biotrophic pathogen without becoming vulnerable to necrotrophic pathogens
Study of the B-site ion behaviour in the multiferroic perovskite bismuth iron chromium oxide
A simple, near-ambient pressure solid-state method was developed to nominally synthesize
BiFe0.5Cr0.5O3. The procedure allowed the gram-scale production of multiferroic samples with
appreciable purity and large amounts of Cr incorporation that were suitable for systematic structural investigation by neutron, X-ray, and electron diffraction in tandem with physical characterization of magnetic and ferroelectric properties. The rhombohedrally distorted perovskite phase was
assigned to the space group R3c by way of X-ray and neutron powder diffraction analysis. Through
a combination of magnetometry and muon spin relaxation, it is evident that there is magnetic ordering in the BFCO phase consistent with G-type antiferromagnetism and a TN 400 K. There is no
clear evidence for chemical ordering of Fe and Cr in the B-site of the perovskite structure and this
result is rationalized by density functional theory and bond valence simulations that show a lowered energy associated with a B-site disordered structure. We believe that our contribution of a
new, low-complexity method for the synthesis of BFO type samples, and dialogue about realising
certain types of ordering in oxide perovskite systems, will assist in the further development of
multiferroics for next-generation devices. Published by AIP Publishing.
https://doi.org/10.1063/1.5020305B.R.M., J.L., A.B., D.L.C., T.L., R.L.W., N.N., and
Y.L. acknowledge the support of the Australian Research
Council (ARC) in the form of Discovery Projects (No.
DP160104780). A.B., D.L.C., N.N., D.Y. and authors thank
the Australian Nuclear Science and Technology
Organisation (ANSTO) for facilities and financial support
and also thank the Echidna instrument scientists for their
expertise
Tumour-retained activated CCR7<sup>+</sup> dendritic cells are heterogeneous and regulate local anti-tumour cytolytic activity
Tumour dendritic cells (DCs) internalise antigen and upregulate CCR7, which directs their migration to tumour-draining lymph nodes (dLN). CCR7 expression is coupled to an activation programme enriched in regulatory molecule expression, including PD-L1. However, the spatio-temporal dynamics of CCR7+ DCs in anti-tumour immune responses remain unclear. Here, we use photoconvertible mice to precisely track DC migration. We report that CCR7+ DCs are the dominant DC population that migrate to the dLN, but a subset remains tumour-resident despite CCR7 expression. These tumour-retained CCR7+ DCs are phenotypically and transcriptionally distinct from their dLN counterparts and heterogeneous. Moreover, they progressively downregulate the expression of antigen presentation and pro-inflammatory transcripts with more prolonged tumour dwell-time. Tumour-residing CCR7+ DCs co-localise with PD-1+CD8+ T cells in human and murine solid tumours, and following anti-PD-L1 treatment, upregulate stimulatory molecules including OX40L, thereby augmenting anti-tumour cytolytic activity. Altogether, these data uncover previously unappreciated heterogeneity in CCR7+ DCs that may underpin a variable capacity to support intratumoural cytotoxic T cells.</p
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Salicylic acid receptors activate jasmonic acid signalling through a non-canonical pathway to promote effector-triggered immunity.
It is an apparent conundrum how plants evolved effector-triggered immunity (ETI), involving programmed cell death (PCD), as a major defence mechanism against biotrophic pathogens, because ETI-associated PCD could leave them vulnerable to necrotrophic pathogens that thrive on dead host cells. Interestingly, during ETI, the normally antagonistic defence hormones, salicylic acid (SA) and jasmonic acid (JA) associated with defence against biotrophs and necrotrophs respectively, both accumulate to high levels. In this study, we made the surprising finding that JA is a positive regulator of RPS2-mediated ETI. Early induction of JA-responsive genes and de novo JA synthesis following SA accumulation is activated through the SA receptors NPR3 and NPR4, instead of the JA receptor COI1. We provide evidence that NPR3 and NPR4 may mediate this effect by promoting degradation of the JA transcriptional repressor JAZs. This unique interplay between SA and JA offers a possible explanation of how plants can mount defence against a biotrophic pathogen without becoming vulnerable to necrotrophic pathogens
Electric-field-induced AFE-FE transitions and associated strain/preferred orientation in antiferroelectric PLZST
Electric-field-induced, antiferroelectric-ferroelectric (AFE-FE) phase transitions are common for AFE materials. To date, the strain and preferred orientation evolution as well as the role of the intermediate FE state during the successive AFE-FE-AFE phase transitions has not been clear. To this end, we have herein studied a typical AFE Pb0.97La0.02(Zr0.56Sn0.33Ti0.11)O3 (PLZST) material using in-situ neutron diffraction. It is striking that the AFE-FE phase transition is not fully reversible: in the electric-field-induced FE state, the induced strain exhibits an elliptical distribution, which in turn leads to significant preferred orientation in the final AFE state after withdrawal of the applied electric-field. The ω-dependent neutron diffraction patterns show clear evidence of the induced strain distribution and associated preferred orientation arising from the AFE-FE phase transition. The current work also provides an explanation for several temperature and electric-field dependent dielectric anomalies as well as unrecovered strain change which appear in AFE materials after exposure to sufficiently high electric fields
Study of the B-site ion behaviour in the multiferroic perovskite bismuth iron chromium oxide
A simple, near-ambient pressure solid-state method was developed to nominally synthesize BiFe0.5Cr0.5O3. The procedure allowed the gram-scale production of multiferroic samples with appreciable purity and large amounts of Cr incorporation that were suitable for systematic structural investigation by neutron, X-ray, and electron diffraction in tandem with physical characterization of magnetic and ferroelectric properties. The rhombohedrally distorted perovskite phase was assigned to the space group R3c by way of X-ray and neutron powder diffraction analysis. Through a combination of magnetometry and muon spin relaxation, it is evident that there is magnetic ordering in the BFCO phase consistent with G-type antiferromagnetism and a TN ∼ 400 K. There is no clear evidence for chemical ordering of Fe and Cr in the B-site of the perovskite structure and this result is rationalized by density functional theory and bond valence simulations that show a lowered energy associated with a B-site disordered structure. We believe that our contribution of a new, low-complexity method for the synthesis of BFO type samples, and dialogue about realising certain types of ordering in oxide perovskite systems, will assist in the further development of multiferroics for next-generation devices
Time-Disordered Crystal Structure of AlPO4-5
Modern ab initio calculations have become increasingly accurate for predicting the symmetry of crystal structures; however, the standard methods usually only determine the 0 K static configuration and therefore misrepresent structures where dynamics play a key role. In this work, we demonstrate a clear experimental example of this phenomenon in the AlPO4-5 molecular sieve where the average high-symmetry P6cc structure emerges from local dynamics involving corner-sharing tetrahedra. Quasielastic and inelastic neutron scattering experiments were conducted to clarify the thermally activated motions between 1.5 and 300 K. Through comparison with ab initio molecular dynamics, we explain why the theoretically predicted structure is not observed in diffraction experiments. Instead, the results indicate this material is an inorganic analogue of a plastic crystal where thermal dynamics dictate the average symmetry.D. L. Cortie thanks Ramzi Kutteh for helpful discussions. Yun
Liu acknowledges the support of the Australian Research
Council. B. R. McBride is supported by an Australian
Government Research Training Program (RTP) Scholarship
Rapid functional impairment of natural killer cells following tumor entry limits anti-tumor immunity
Immune cell dysfunction within the tumor microenvironment (TME) undermines the control of cancer progression. Established tumors contain phenotypically distinct, tumor-specific natural killer (NK) cells; however, the temporal dynamics, mechanistic underpinning and functional significance of the NK cell compartment remains incompletely understood. Here, we use photo-labeling, combined with longitudinal transcriptomic and cellular analyses, to interrogate the fate of intratumoral NK cells. We reveal that NK cells rapidly lose effector functions and adopt a distinct phenotypic state with features associated with tissue residency. NK cell depletion from established tumors did not alter tumor growth, indicating that intratumoral NK cells cease to actively contribute to anti-tumor responses. IL-15 administration prevented loss of function and improved tumor control, generating intratumoral NK cells with both tissue-residency characteristics and enhanced effector function. Collectively, our data reveals the fate of NK cells after recruitment into tumors and provides insight into how their function may be revived