Dicer controls CD8⁺T-cell activation, migration, and survival

Abstract

Reading out the temperature-memory of polymers, which is their ability to remember the temperature where they were deformed recently, is thus far unavoidably linked to erasing this memory effect. Here temperature-memory polymer actuators (TMPAs) based on cross-linked copolymer networks exhibiting a broad melting temperature range (ΔT m ) are presented, which are capable of a long-term temperature-memory enabling more than 250 cyclic thermally controlled actuations with almost constant performance. The characteristic actuation temperatures T act s of TMPAs can be adjusted by a purely physical process, guiding a directed crystallization in a temperature range of up to 40°C by variation of the parameter T sep in a nearly linear correlation. The temperature T sep divides ΔT m into an upper T m range (T > T sep ) forming a reshapeable actuation geometry that determines the skeleton and a lower T m range (T < T sep ) that enables the temperature-controlled bidirectional actuation by crystallization-induced elongation and melting-induced contraction. The macroscopic bidirectional shape changes in TMPAs could be correlated with changes in the nanostructure of the crystallizable domains as a result of in situ Xray investigations. Potential applications of TMPAs include heat engines with adjustable rotation rate and active building facades with self-regulating sun protectors.reversible shape-memory polymer | active movement T he alignment and coupling of thermally controlled volume changes on the nanoscale has emerged as most important working principle to translate shape changes from the nanolevel to the macrolevel in polymers (1-4). In stimuli-responsive polymers capable of a free-standing shape-changing effect, this alignment is achieved during synthesis or processing by either application of external stress or the utilization of templates and fixed by covalent cross-links (5-12). Once synthesis is completed, the geometry of the shape change cannot be changed anymore (13-15) and the actuation temperature is fixed; this relies on thermal transitions with a defined temperature. Here we explored whether it is possible to implement a thermally controlled bidirectional actuation into free-standing polymers by purely physical manipulation enabling to adjust (repeatedly) the actuation temperature and (shape changing) geometry.Although programmable shape changes have been realized in shape-memory polymers (SMPs), this effect is generally a onetime, one-way effect in free-standing SMPs (16-18). In SMPs the switching domains, which can solidify by crystallization or vitrification, provide two functions: they determine the geometry of the shape change and cause the entropy elastic recovery. A reversible movement could be observed when polymers with crystallizable segments are held under an externally applied constant stress (3,8). Recently temperature-memory polymers (TMPs) enabled the programming of the switching temperature (19,20). Also this temperature-memory effect (TME) is limited to a onetime, one-way effect. The aim of th...

microRNA-301a regulation of a T-helper 17 immune response controls autoimmune demyelination

“…34). Recently, Mir-301a has been reported as being expressed in response to activation in CD8 + T cells, where it probably plays a role as a regulator of CD69 expression (35). miR-301a also has been identified among the miRNA enriched in Th1 and Th2 populations (36).…”

microRNAs function in CD8+T cell biology

“…In addition, a deficiency of Dicer results in a significant decrease in the number of CD8 + T cells in blood and liver during L. monocytogenes infection, and this is shown to stem from impaired downregulation of CD69 expression on the surface of Dicer-deficient CD8 + T cells that has been linked to the defective migration of activated effector cells out of lymphoid tissues. At least 1 specific miRNA family-miRNA-130/301-has been found to be functionally important in this process, as the overexpression of miR-130/301 in Dicer-deficient CD8 + T cells reverses the CD69 retention phenotype to a certain degree [36]. CD8 + T cell responses can be influenced indirectly by miRNAs in immune cells other than T cells.…”

“…To circumvent any complications from defective thymocyte development in the absence of miRNAs, several groups have generated Dicerdeficient, mature CD8 + T cells, and their results showed that deficiency of Dicer leads to a decrease in the frequency and numbers of CD8 + T cells in vivo following virus infections [36,37]. Intriguingly, Dicer seems to impair initial CD8 + T cell activation and proliferation, as suggested in in vitro experiments showing that Dicer-deficient CD8 + T cells revealed a surprising increase in cell=cycle entry upon TCR stimulation.…”

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

“…Dicer is required for CD8 + Tcell survival and accumulation, but not required for the early steps in CD8 + Tcell activation [104,105] . Dicer and miRNAs such as miR139 and miR150 also participate in controlling the cytolytic program, as well as other programs of effector cytotoxic T lymphocyte differentiation [106] .…”