Biology subjects

Melo, G. A.

Publications and source records attributed to Melo, G. A..

3 recordsLinked to original sources

bioRxiv2022

Polycomb Repressive Complex 1 subunit Cbx4 positively regulates effector responses in CD8 T cells

CD8 T cell differentiation is controlled by the crosstalk of various transcription factors and epigenetic modulators. Uncovering the different players in regulating this process is fundamental to improving immunotherapy and designing novel therapeutic approaches. Here, we show that Polycomb Repressive Complex (PRC)1 subunit Chromobox (Cbx)4 favors differentiation to effector CD8 T cells. Cbx4 deficiency in CD8 T cells induced transcriptional signature and phenotype of memory cells, increasing the formation of memory population during acute viral infection. It has been previously shown that besides chromodomain-mediated binding to H3K27me3, Cbx4 function as a SUMO E3 ligase in a SUMO interacting motifs (SIM)-dependent way. The overexpression of Cbx4 mutants in distinct domains showed that this protein regulates CTL differentiation primarily in a SIM-dependent way and partially through its chromodomain. Our data revealed a novel role of a Polycomb group protein Cbx4 controlling CD8 T lymphocyte differentiation and indicates the SUMOylation process as a key molecular mechanism connected to chromatin modification in this process. SummaryUnderstanding the epigenetic control of CTL differentiation is critical for the manipulation of these cells in immunotherapy protocols. This article demonstrates a novel role for Cbx4, a Polycomb-group protein, in supporting CD8 T cell commitment to an effector cell phenotype.

immunology↗

bioRxiv2021

Cytotoxic CD4+ T cells driven by T-cell intrinsic IL-18R/MyD88 signaling predominantly infiltrate Trypanosoma cruzi-infected hearts

Increasing attention has been directed to cytotoxic CD4+ T cells (CD4CTLs) in different pathologies, both in humans and mice. The impact of CD4CTLs in immunity and the mechanisms controlling their generation, however, remain poorly understood. Here, we show that CD4CTLs abundantly differentiate during mouse infection with the intracellular parasite Trypanosoma cruzi. CD4CTLs display parallel kinetics to Th1 cells in the spleen, mediate specific cytotoxicity against cells presenting pathogen-derived antigens and express immunoregulatory and/or exhaustion markers. We demonstrate that CD4CTL absolute numbers and activity are severely reduced in both Myd88-/- and Il18ra-/- mice. Of note, the infection of mixed-bone marrow chimeras revealed that WT but not Myd88-/- cells transcribe the CD4CTL gene signature and that Il18ra-/- and Myd88-/- CD4+ T cells phenocopy each other. Moreover, adoptive transfer of WT CD4+GzB+ T cells to infected Il18ra-/- mice extended their survival. Importantly, cells expressing the CD4CTL phenotype predominate among CD4+ T cells infiltrating the infected mouse cardiac tissue and are increased in the blood of Chagas patients, in which the frequency of CD4CTLs correlates with the severity of cardiomyopathy. Our findings describe CD4CTLs as a major player in immunity to a relevant human pathogen and disclose T-cell intrinsic IL-18R/MyD88 signaling as a key pathway controlling the magnitude of the CD4CTL response.

immunology↗

bioRxiv2017

Paleocene origin of the Neotropical lineage of cleptoparasitc bees Ericrocidini-Rhathymini (Hymenoptera, Apidae)

Cleptoparasitic bees abandoned the pollen collecting for their offspring and lay their eggs on other bees provisioned nests. Also known as cuckoo bees they belong to several lineages, especially diverse in Apinae. We focused on a lineage of Apinae cleptoparasitic bees, the clade Ericrocidini+Rhathymini, which attack nests of the oil-collecting bees. We sequenced five genes for a broad sampling in this clade plus a large outgroup and reconstruct phylogeny and divergence times. We confirmed the monophyly of the clade Ericrocidini+Rhathymini and its position inside the ericrocidine line, together with the tribes Protepeolini, Isepeolini and Coelioxoidini. Our results corroborate the current taxonomic classification. Ericrocis is the basal most lineage in Ericrocidini and the position of Acanthopus and the most diverse genus Mesoplia were inconclusive. Ericrocidini+Rhathymini diverged from Parepeolus aterrimus 74 mya in the Cretaceous. Considering the robust molecular evidence of their sister relationships, the striking differences on the first instar larvae morphology of the two groups are probably adaptations to the distinct nesting biology of their hosts. As other parasites in the ericrocidine line, both groups possess larvae adapted to kill the immature host and to feed on floral oil provisioned by the host female. The evolution of host specialization in the line Ericrocidini+Rhathymini retroced to the Eocene when they arose synchronously with their hosts, Centris and Epicharis.

evolutionary biology↗