Search bioRxiv⌕ Search

Biology subjects

MacKenzie, R.

Publications and source records attributed to MacKenzie, R..

2 recordsLinked to original sources

Quantification and uncertainty of root growth stimulation by elevated CO2 in mature temperate deciduous forest

Increasing CO2 levels are a major global challenge, and the extent to which increasing anthropogenic CO2 emissions can be mitigated by natural carbon sinks remains poorly understood. The uptake of elevated CO2 (eCO2) by the terrestrial biosphere, and subsequent sequestration as biomass in ecosystems, may act as a negative feedback in the carbon budget, but remains hard to quantify in natural ecosystems. Here, we combine large-scale field observations of fine root stocks and flows, derived from belowground imaging and soil cores, with image analysis, stochastic modelling, and statistical inference, to elucidate belowground root dynamics in a mature temperate deciduous forest under free-air CO2 enrichment to 150ppm above ambient levels. Using over 67k frames of belowground observation, we observe that eCO2 leads to relatively faster root production (a peak volume fold change of 4.52 {+/-} 0.44 eCO2 versus 2.58 {+/-} 0.21 control). We identify an increase in existing root elongation relative to root mass decay as the likely causal mechanism for this acceleration. Direct physical analysis of biomass and width measurements from 552 root systems recovered from soil cores support this picture, with lengths and widths of fine roots significantly increasing under eCO2. We use dynamic measurements to estimate fine root contributions to net primary productivity, finding an increase under eCO2, with an estimated mean annual 204 {+/-} 93 g dw m-2yr-1 eCO2 versus 140 {+/-} 60 g dw m-2 yr-1 control. We also quantify and discuss the uncertainties in such productivity measurements. This multi-faceted approach thus sheds quantitative light on the challenging characterisation of the eCO2 response of root biomass in mature temperate forests.

plant biology↗

The MS remyelinating drug bexarotene (an RXR agonist) promotes induction of human Tregs and suppresses Th17 differentiation in vitro

The retinoid X receptor (RXR) agonist bexarotene has recently been shown to promote remyelination in individuals with multiple sclerosis. Murine studies demonstrated that RXR agonists can have anti-inflammatory effects by enhancing the ability of all-trans-retinoic acid (tRA), the primary active metabolite of vitamin A, to promote T regulatory cell (Treg) induction and reduce Th17 differentiation in vitro, following stimulation of naive CD4 cells in the presence of TGF-{beta}. Stimulating naive human CD4 T cells for 7 days, in the presence of either Treg or Th17 skewing cytokines {+/-} bexarotene (1 M), {+/-} other RXR agonists (9CisRA and NRX 194204), or {+/-} tRA (100 nM) shows that RXR agonists, including bexarotene, are capable of tipping the human Treg/Th17 axis in favour of Treg induction. Furthermore, this occurs independently of tRA and retinoic acid receptor (RAR) signalling. Tregs induced in the presence of bexarotene express many of the canonical markers of T cell regulation and are functionally suppressive in vitro. These findings support a potential immunomodulatory role for bexarotene and highlight the possible therapeutic application of RXR agonists in autoimmune disease, with bexarotenes pro-remyelinating effects making multiple sclerosis a particularly attractive disease target. Significance StatementThe pan-retinoid X receptor (RXR) agonist bexarotene has recently been shown to promote remyelination in patients with multiple sclerosis. Here we demonstrate that bexarotene, and other RXR agonists have immunomodulating effects, tipping the Th17/T regulatory cell (Treg) differentiation axis in favour of Treg development. These findings lend support to the idea of developing RXR agonists as treatments of autoimmune diseases, in particular multiple sclerosis.

immunology↗