Annexin V expression on CD4<sup>+</sup> T cells with regulatory function

Bollinger, A.; Bollinger, Thomas; Rupp, Jan; Shima, Kensuke; Gross, Natalie; Padayachy, Laura; Chicheportiche, Rachel; Yung, Gisella Puga

doi:10.1111/imm.13140

Cited by 4 publications

(3 citation statements)

References 77 publications

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“…Additionally, annexin B11 ( AnxB11 ) was also upregulated in the bacteriomes of both species. Mammalian annexins are inhibitors of immune responses, where they suppress inflammatory responses during apoptosis [ 99 , 100 ]. This observation further supports a more tolerant microenvironment in both tsetse species G. brevipalpis and G. morsitans likely aimed to sustain high bacterial densities within bacteriomes when compared to midguts.…”

Section: Resultsmentioning

confidence: 99%

The holobiont transcriptome of teneral tsetse fly species of varying vector competence

et al. 2021

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Background Tsetse flies are the obligate vectors of African trypanosomes, which cause Human and Animal African Trypanosomiasis. Teneral flies (newly eclosed adults) are especially susceptible to parasite establishment and development, yet our understanding of why remains fragmentary. The tsetse gut microbiome is dominated by two Gammaproteobacteria, an essential and ancient mutualist Wigglesworthia glossinidia and a commensal Sodalis glossinidius. Here, we characterize and compare the metatranscriptome of teneral Glossina morsitans to that of G. brevipalpis and describe unique immunological, physiological, and metabolic landscapes that may impact vector competence differences between these two species. Results An active expression profile was observed for Wigglesworthia immediately following host adult metamorphosis. Specifically, ‘translation, ribosomal structure and biogenesis’ followed by ‘coenzyme transport and metabolism’ were the most enriched clusters of orthologous genes (COGs), highlighting the importance of nutrient transport and metabolism even following host species diversification. Despite the significantly smaller Wigglesworthia genome more differentially expressed genes (DEGs) were identified between interspecific isolates (n = 326, ~ 55% of protein coding genes) than between the corresponding Sodalis isolates (n = 235, ~ 5% of protein coding genes) likely reflecting distinctions in host co-evolution and adaptation. DEGs between Sodalis isolates included genes involved in chitin degradation that may contribute towards trypanosome susceptibility by compromising the immunological protection provided by the peritrophic matrix. Lastly, G. brevipalpis tenerals demonstrate a more immunologically robust background with significant upregulation of IMD and melanization pathways. Conclusions These transcriptomic differences may collectively contribute to vector competence differences between tsetse species and offers translational relevance towards the design of novel vector control strategies.

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Section: Resultsmentioning

confidence: 99%

The holobiont transcriptome of teneral tsetse fly species of varying vector competence

et al. 2021

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“…When studied by GSEA, CD4 + T cells from AML patients were enriched of signatures related to regulatory T (Treg) cells (Figure 5E). Of note, some ADM coexpressed genes, including JUNB, CDKN1A, ANXA5, CYBB, NFKBIZ, that were upregulated in CD4 + T cells from AML patients compared with cells from healthy controls (Figure 5B), are known to participate to the Treg phenotype (65)(66)(67)(68)(69).…”

Section: The Adm Gene Network Is Enriched Of Inflammatory Signatures In Leukemic Cells and Of Immunomodulatory Genes In T Cells From Aml mentioning

confidence: 99%

Adrenomedullin Expression Characterizes Leukemia Stem Cells and Associates With an Inflammatory Signature in Acute Myeloid Leukemia

et al. 2021

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Adrenomedullin (ADM) is a hypotensive and vasodilator peptide belonging to the calcitonin gene-related peptide family. It is secreted in vitro by endothelial cells and vascular smooth muscle cells, and is significantly upregulated by a number of stimuli. Moreover, ADM participates in the regulation of hematopoietic compartment, solid tumors and leukemias, such as acute myeloid leukemia (AML). To better characterize ADM involvement in AML pathogenesis, we investigated its expression during human hematopoiesis and in leukemic subsets, based on a morphological, cytogenetic and molecular characterization and in T cells from AML patients. In hematopoietic stem/progenitor cells and T lymphocytes from healthy subjects, ADM transcript was barely detectable. It was expressed at low levels by megakaryocytes and erythroblasts, while higher levels were measured in neutrophils, monocytes and plasma cells. Moreover, cells populating the hematopoietic niche, including mesenchymal stem cells, showed to express ADM. ADM was overexpressed in AML cells versus normal CD34+ cells and in the subset of leukemia compared with hematopoietic stem cells. In parallel, we detected a significant variation of ADM expression among cytogenetic subgroups, measuring the highest levels in inv(16)/t(16;16) or complex karyotype AML. According to the mutational status of AML-related genes, the analysis showed a lower expression of ADM in FLT3-ITD, NPM1-mutated AML and FLT3-ITD/NPM1-mutated cases compared with wild-type ones. Moreover, ADM expression had a negative impact on overall survival within the favorable risk class, while showing a potential positive impact within the subgroup receiving a not-intensive treatment. The expression of 135 genes involved in leukemogenesis, regulation of cell proliferation, ferroptosis, protection from apoptosis, HIF-1α signaling, JAK-STAT pathway, immune and inflammatory responses was correlated with ADM levels in the bone marrow cells of at least two AML cohorts. Moreover, ADM was upregulated in CD4+ T and CD8+ T cells from AML patients compared with healthy controls and some ADM co-expressed genes participate in a signature of immune tolerance that characterizes CD4+ T cells from leukemic patients. Overall, our study shows that ADM expression in AML associates with a stem cell phenotype, inflammatory signatures and genes related to immunosuppression, all factors that contribute to therapy resistance and disease relapse.

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“…Studies by Fischer et al(15) observed that Ag stimulation of CD4 1 T cells led to the transient externalization of PS and that treatment with Annexin V diminished proinflammatory cytokine secretion. Moreover, Bollinger et al(46)…”

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confidence: 99%

Phosphatidylserine-Targeting Monoclonal Antibodies Exhibit Distinct Biochemical and Cellular Effects on Anti-CD3/CD28–Stimulated T Cell IFN-γ and TNF-α Production

Calianese

Kreiss

Kasikara

et al. 2021

The Journal of Immunology

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Phosphatidylserine (PS)-targeting monoclonal Abs (mAbs) that directly target PS and target PS via β2-gp1 (β2GP1) have been in preclinical and clinical development for over 10 y for the treatment of infectious diseases and cancer. Although the intended targets of PS-binding mAbs have traditionally included pathogens as well as stressed tumor cells and its associated vasculature in oncology, the effects of PS-targeting mAbs on activated immune cells, notably T cells, which externalize PS upon Ag stimulation, is not well understood. Using human T cells from healthy donor PBMCs activated with an anti-CD3 + anti-CD28 Ab mixture (anti-CD3/CD28) as a model for TCR-mediated PS externalization and T cell stimulation, we investigated effects of two different PS-targeting mAbs, 11.31 and bavituximab (Bavi), on TCR activation and TCR-mediated cytokine production in an ex vivo paradigm. Although 11.31 and Bavi bind selectivity to anti-CD3/28 activated T cells in a PS-dependent manner, surprisingly, they display distinct functional activities in their effect on IFN-γ and TNF-ɑ production, whereby 11.31, but not Bavi, suppressed cytokine production. This inhibitory effect on anti-CD3/28 activated T cells was observed on both CD4+ and CD8+ cells and independently of monocytes, suggesting the effects of 11.31 were directly mediated by binding to externalized PS on activated T cells. Imaging showed 11.31 and Bavi bind at distinct focal depots on the cell membrane. Collectively, our findings indicate that PS-targeting mAb 11.31 suppresses cytokine production by anti-CD3/28 activated T cells.

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Annexin V expression on CD4⁺ T cells with regulatory function

Cited by 4 publications

References 77 publications

The holobiont transcriptome of teneral tsetse fly species of varying vector competence

The holobiont transcriptome of teneral tsetse fly species of varying vector competence

Adrenomedullin Expression Characterizes Leukemia Stem Cells and Associates With an Inflammatory Signature in Acute Myeloid Leukemia

Phosphatidylserine-Targeting Monoclonal Antibodies Exhibit Distinct Biochemical and Cellular Effects on Anti-CD3/CD28–Stimulated T Cell IFN-γ and TNF-α Production

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Annexin V expression on CD4+ T cells with regulatory function

Cited by 4 publications

References 77 publications

The holobiont transcriptome of teneral tsetse fly species of varying vector competence

The holobiont transcriptome of teneral tsetse fly species of varying vector competence

Adrenomedullin Expression Characterizes Leukemia Stem Cells and Associates With an Inflammatory Signature in Acute Myeloid Leukemia

Phosphatidylserine-Targeting Monoclonal Antibodies Exhibit Distinct Biochemical and Cellular Effects on Anti-CD3/CD28–Stimulated T Cell IFN-γ and TNF-α Production

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Annexin V expression on CD4⁺ T cells with regulatory function