Biology subjects

Rubino, V.

Publications and source records attributed to Rubino, V..

3 recordsLinked to original sources

bioRxiv2024

Low abundant intestinal commensals modulate immune control of chronic myeloid leukemia stem cells

Leukemia stem cells (LSCs) are resistant to therapy and immune control. The reason for their resistance to elimination by cytotoxic T cells (CTLs) remains unclear. This study shows that specific low abundant Gram-negative intestinal commensals of the genus Sutterella suppress the anti-leukemia immune response in chronic myeloid leukemia (CML). We found that germ-free and specific opportunistic pathogen-free (SOPF) mice are protected from CML development and that colonization of SOPF mice with Sutterella wadsworthensis, but not other related and unrelated bacterial strains, rescues CML development. A higher prevalence of this microbe resulted in Myd88/TRIF-mediated CTL exhaustion in SPF compared to SOPF CML mice as evidenced by higher surface expression of exhaustion markers on CTLs, a reduced capacity to produce interferon-gamma and granzyme B and to kill LSCs in vitro. These findings provide new insights into the immune control of LSCs and identify Sutterella species as regulators of anti-leukemic immunity in CML.

cancer biology↗

bioRxiv2023

CD4+ T cell-derived IL21 regulates stem cell fate in acute myeloid leukemia by activation of p38-MAPK signaling

Self-renewal programs in leukemia stem cells (LSCs) predict poor prognosis in acute myeloid leukemia (AML) patients. We identified CD4+ T cell-derived interleukin (IL) 21 as an important negative regulator of self-renewal of murine and human LSCs, but not hematopoietic stem cells. IL21/IL21R signaling favored asymmetric cell division and differentiation in LSCs through accumulation of reactive oxygen species (ROS) and activation of p38-MAPK signaling, resulting in reduced LSCs number and significantly prolonged survival in murine AML models. In human AML, serum IL21 at diagnosis was identified as an independent positive prognostic biomarker for outcome and correlated with better survival and higher complete remission rate in patients that underwent high-dose chemotherapy. IL21 inhibited primary AML LSCs function in vitro by activating ROS and p38-MAPK signaling and this effect was enhanced by cytarabine treatment. Consequently, promoting IL21/IL21R signaling on LSCs may be a novel approach to decrease stemness and increase differentiation in AML.

cancer biology↗

bioRxiv2020

Multiple spatial codes for navigating 2-D semantic spaces

When mammals navigate in the physical environment, specific neurons such as grid-cells, head-direction cells, and place-cells activate to represent the navigable surface, the faced direction of movement, and the specific location the animal is visiting. Here we test the hypothesis that these codes are also activated when humans navigate abstract language-based representational spaces. Human participants learnt the meaning of novel words as arbitrary signs referring to specific artificial audiovisual objects varying in size and sound. Next, they were presented with sequences of words and asked to process them semantically while we recorded the activity of their brain using fMRI. Processing words in sequence was conceivable as movements in the semantic space, thus enabling us to systematically search for the different types of neuronal coding schemes known to represent space during navigation. By applying a combination of representational similarity and fMRI-adaptation analyses, we found evidence of i) a grid-like code in the right postero-medial entorhinal cortex, representing the general bidimensional layout of the novel semantic space; ii) a head-direction-like code in parietal cortex and striatum, representing the faced direction of movements between concepts; and iii) a place-like code in medial prefrontal, orbitofrontal, and mid cingulate cortices, representing the Euclidean distance between concepts. We also found evidence that the brain represents 1-dimensional distances between word meanings along individual sensory dimensions: implied size was encoded in secondary visual areas, and implied sound in Heschls gyrus/Insula. These results reveal that mentally navigating between 2D word meanings is supported by a network of brain regions hosting a variety of spatial codes, partially overlapping with those recruited for navigation in physical space.

neuroscience↗