1,720,983 research outputs found
Understanding human NK cell differentiation: Clues for improving the haploidentical hematopoietic stem cell transplantation
No full textMethylprednisolone induces preferential and rapid differentiation of CD34+ cord blood precursors toward NK cells.
No full textPrevious studies showed that methylprednisolone (MePDN) down-regulates the surface expression of
activating NK receptors and sharply inhibits the NK cytotoxicity both in vitro and in vivo. Since
MePDN is administered to patients undergoing hemopoietic stem cell transplant to treat acute graft
versus host disease (GvHD), we analyzed whether it could also inhibit the NK cell differentiation from
CD341 hemopoietic cell precursors, thus interfering with the development of effector cells with antileukemic
potential. We show that MePDN promotes the in vitro differentiation of CD1611CD561/2
immature NK cells by inducing a rapid expression of NKp46, NKG2D, DNAX-accessory molecule 1
(DNAM-1), leukocyte function-associated antigen-1 and NKG2A and an efficient cytolytic activity. This
phenotypic and functional NK cell maturation occurred more rapidly than in parallel control cultures
performed in the absence of MePDN. In addition, MePDN induced CD331CD1612CD562 myeloid
precursors to switch toward NK cells. It is also of note that immature NK cells when cultured in the
absence (but not in the presence) of MePDN produced high amounts of IL-8. These data indicate that
MePDN can accelerate the in vitro NK cell differentiation, thus revealing a dichotomous effect on
immature versus mature NK cells; in addition, interference with the in vitro development of myeloid
cells occurred. These effects should be further investigated in hemopoietic stem cell transplanted
patients receiving steroids to treat GvHD
Human innate lymphoid cells
No full textThe interest in innate lymphoid cells (ILC) has rapidly grown during the last decade. ILC include distinct cell types that are collectively involved in host protection against pathogens and tumor cells and in the regulation of tissue homeostasis. Studies in mice enabled a broad characterization of ILC function and of their developmental requirements. In humans all mature ILC subsets have been characterized and their role in the pathogenesis of certain disease is emerging. Nonetheless, still limited information is available on human ILC development. Indeed, only the cell precursors committed towards NK cells or ILC3 have been described. Here, we review the most recent finding on human mature ILC, discussing their tissue localization and function. Moreover, we summarize the available data regarding human ILC development
MSC and innate immune cell interactions: A lesson from human decidua
No full textBoth experimental and clinical studies revealed that stromal cells (SC) are present in decidua (DSC) and placenta (PSC) at the early and late phase of pregnancy, respectively, and they may contribute to the induction of an anti-inflammatory/tolerogenic microenvironment crucial for the establishment/maintenance of successful pregnancy. These cells share common features with mesenchymal SC. In the present contribution, we provide an overall view on DSC features and on their ability to recruit NK cells and to regulate both differentiation and function not only of NK cells but also of CD14+ myeloid cells. NK cells represent the large majority of leukocytes populating decidual tissues during the first trimester of pregnancy. Their cross-talk with DSC is thought to play a key role in the establishment of feto-maternal tolerance. We also discuss recent data suggesting that DSC may contribute to tissue remodeling, placentation, and recruitment of leukocytes also through their interaction with innate lymphoid cells (ILC) such as ILC3, that have recently been shown to be present in decidual tissue
Effect of tyrosin kinase inhibitors on NK Cell and ILC3 development and function
No full textTyrosin kinase inhibitors (TKI) sharply improved the prognosis of Chronic Myeloid Leukemia (CML) and of Philadelphia+ Acute Lymphoblastic Leukemia (Ph+ALL) patients. However, TKI are not curative because of the development of resistance and lack of complete molecular remission in the majority of patients. Clinical evidences would support the notion that patient's immune system may play a key role in preventing relapses. In particular, increased proportions of terminally differentiated CD56+CD16+CD57+ NK cells have been reported to be associated with successful Imatinib therapy discontinuation or with a deep molecular response in Dasatinib-treated patients. In view of the potential role of NK cells in immune-response against CML, it is important to study whether any TKI have an effect on the NK cell development and identify possible molecular mechanism(s) by which continuous exposure to in vitro TKI may influence NK cell development and repertoire. To this end, CD34+ hematopoietic stem cells (HSC) were cultured in the absence or in the presence of Imatinib, Nilotinib, or Dasatinib. We show that all compounds exert an inhibitory effect on CD56+ cell recovery. In addition, Dasatinib sharply skewed the repertoire of CD56+ cell population, leading to an impaired recovery of CD56+CD117-CD16+CD94/NKG2A+EOMES+ mature cytotoxic NK cells, while the recovery of CD56+CD117+CD94/NKG2A RORγt+ IL-22-producing ILC3 was not affected. This effect appears to involve the Dasatinib-mediated inhibition of Src kinases and, indirectly, of STAT5-signaling activation in CD34+ cells during first days of culture. Our studies, reveal a possible mechanism by which Dasatinib may interfere with the proliferation and maturation of fully competent NK cells, i.e., by targeting signaling pathways required for differentiation and survival of NK cells but not of ILC3
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Analysis of the circulating Th1/Th17 lymphocyte repertoire after hematopoietic stem cell transplant may reveal opportunistic fungal infections rather than GvHD reaction
No full textHuman Th17 lymphocytes have been suggested to play a role in the pathogenesis of Graft versus Host Disease (GvHD). However, their actual involvement has not been clarified so far. We analysed the T cell recovery in the peripheral blood of 30 paediatric patients at different time intervals after allogeneic hematopoietic stem cell transplantation (HSCT).
We investigated the Th1 (CD4+CD161-CXCR3+CCR6-), Th1/Th17 (CD4+CD161+CXCR3+CCR6+) and Th17 (CD4+CD161+CXCR3-CCR6+) cell subsets repertoire in relation with the GVHD onset, the occurrence of opportunistic infections and/or viral reactivation. In the first 90 days after HSCT, we found no significant difference between patients developing or not acute GVHD. On the other hand, patients affected by chronic GVHD display a sharp reduction of circulating CD4+ lymphocytes. In addition, they were significantly enriched in CD4+CD161+. Analysis of cytokine production revealed that chronic GVHD patients display an increased production of IFN-gamma and IL-17. In patients with acute GVHD, increases of IFN-gamma and IL-17 production were statistically significant, however, no correlation could be found between surface phenotype and cytokine production. On the other hand, in four patients a clear correlation could be observed between the onset of Candida infection and increases of circulating IL-17-producing Th17 cells. Th17 increases were transient and paralleled the course of infection.
Our data suggest that chronic GvHD might involve Th1/Th17 cells. More importantly, they show that monitoring Th17 cell populations may provide an useful information on the onset and the severity of opportunistic fungal infections
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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