All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation

We demonstrate that all-trans retinoic acid (RA) induces FoxP3+ adaptive T regulatory cells (A-Tregs) to acquire a gut-homing phenotype (α4β7+ CC chemokine receptor 9+) and the capacity to home to the lamina propria of the small intestine. Under conditions that favor the differentiation of A-Tregs (transforming growth factor–β1 and interleukin 2) in vitro, the inclusion of RA induces nearly all activated CD4+ T cells to express FoxP3 and greatly increases the accumulation of these cells. In the absence of RA, A-Treg differentiation is abruptly impaired by proficient antigen presenting cells or through direct co-stimulation. In the presence of RA, A-Treg generation occurs even in the presence of high levels of co-stimulation, with RA attenuating co-stimulation from interfering from FoxP3 induction. The recognition that RA induces gut imprinting, together with our finding that it enhances A-Treg conversion, differentiation, and expansion, indicates that RA production in vivo may drive both the imprinting and A-Treg development in the face of overt inflammation

In vitro-generated Tc17 cells present a memory phenotype and serve as a reservoir of Tc1 cells in vivo

Indexación: Scopus.Memory CD8+ T cells are ideal candidates for cancer immunotherapy because they can mediate long-term protection against tumors. However, the therapeutic potential of different in vitro-generated CD8+ T cell effector subsets to persist and become memory cells has not been fully characterized. Type 1 CD8+ T (Tc1) cells produce interferon-γ and are endowed with high cytotoxic capacity, whereas IL-17-producing CD8+ T (Tc17) cells are less cytotoxic but display enhanced self-renewal capacity. We sought to evaluate the functional properties of in vitro-generated Tc17 cells and elucidate their potential to become long lasting memory cells. Our results show that in vitro-generated Tc17 cells display a greater in vivo persistence and expansion in response to secondary antigen stimulation compared to Tc1 cells. When transferred into recipient mice, Tc17 cells persist in secondary lymphoid organs, present a recirculation behavior consistent with central memory T cells, and can shift to a Tc1 phenotype. Accordingly, Tc17 cells are endowed with a higher mitochondrial spare respiratory capacity than Tc1 cells and express higher levels of memory-related molecules than Tc1 cells. Together, these results demonstrate that in vitro-generated Tc17 cells acquire a central memory program and provide a lasting reservoir of Tc1 cells in vivo, thus supporting the use of Tc17 lymphocytes in the design of novel and more effective therapies.https://www.frontiersin.org/articles/10.3389/fimmu.2018.00209/ful

Retinoic Acid Generates Regulatory T Cells in Experimental Transplantation

ABSTRACT Regulatory T cells play a key role to inhibit effector lymphocytes, avoid, autoimmunity, and restrain allogeneic immunity. Retinoic acid is an important cofactor that stimulates the generation and expansion of regulatory T cells. Naive T cells, coincubated with allogeneic antigen-presenting cells and retinoic acid, in conjunction with transforming growth factor (TGF) ␤ and interleukin (IL) 2, generated allogeneic regulatory T cells de novo. These cells were able to inhibit skin rejection in adoptive transfer experiments. The generation of regulatory T cells ex vivo with retinoic acid, TGF-␤, and IL-2 represents a new step toward specific regulation of allogeneic immune responses

Charging Effects and Quantum Crossover in Granular Superconductors

The effects of the charging energy in the superconducting transition of granular materials or Josephson junction arrays is investigated using a pseudospin one model. Within a mean-field renormalization-group approach, we obtain the phase diagram as a function of temperature and charging energy. In contrast to early treatments, we find no sign of a reentrant transition in agreement with more recent studies. A crossover line is identified in the non-superconducting side of the phase diagram and along which we expect to observe anomalies in the transport and thermodynamic properties. We also study a charge ordering phase, which can appear for large nearest neighbor Coulomb interaction, and show that it leads to first-order transitions at low temperatures. We argue that, in the presence of charge ordering, a non monotonic behavior with decreasing temperature is possible with a maximum in the resistance just before entering the superconducting phase.Comment: 15 pages plus 4 fig. appended, Revtex, INPE/LAS-00

The demethylase inhibitor GSK-J4 limits inflammatory colitis by promoting de novo synthesis of retinoic acid in dendritic cells

Indexación ScopusDendritic cells (DCs) promote T-cell mediated tolerance to self-antigens and induce inflammation to innocuous-antigens. This dual potential makes DCs fundamental players in inflammatory disorders. Evidence from inflammatory colitis mouse models and inflammatory bowel diseases (IBD) patients indicated that gut inflammation in IBD is driven mainly by T-helper-1 (Th1) and Th17 cells, suggesting an essential role for DCs in the development of IBD. Here we show that GSK-J4, a selective inhibitor of the histone demethylase JMJD3/UTX, attenuated inflammatory colitis by reducing the inflammatory potential and increasing the tolerogenic features of DCs. Mechanistic analyses revealed that GSK-J4 increased activating epigenetic signals while reducing repressive marks in the promoter of retinaldehyde dehydrogenase isoforms 1 and 3 in DCs, enhancing the production of retinoic acid. This, in turn, has an impact on regulatory T cells (Treg) increasing their lineage stability and gut tropism as well as potentiating their suppressive activity. Our results open new avenues for the treatment of IBD patients. © 2021, The Author(s).https://www-nature-com.recursosbiblioteca.unab.cl/articles/s41598-020-79122-

Bone marrow cell trafficking following intravenous administration

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75122/1/j.1365-2141.1999.01779.x.pd

In Vitro-Generated Tc17 Cells Present a Memory Phenotype and Serve As a Reservoir of Tc1 Cells In Vivo

Memory CD8+ T cells are ideal candidates for cancer immunotherapy because they can mediate long-term protection against tumors. However, the therapeutic potential of different in vitro-generated CD8+ T cell effector subsets to persist and become memory cells has not been fully characterized. Type 1 CD8+ T (Tc1) cells produce interferon-γ and are endowed with high cytotoxic capacity, whereas IL-17-producing CD8+ T (Tc17) cells are less cytotoxic but display enhanced self-renewal capacity. We sought to evaluate the functional properties of in vitro-generated Tc17 cells and elucidate their potential to become long lasting memory cells. Our results show that in vitro-generated Tc17 cells display a greater in vivo persistence and expansion in response to secondary antigen stimulation compared to Tc1 cells. When transferred into recipient mice, Tc17 cells persist in secondary lymphoid organs, present a recirculation behavior consistent with central memory T cells, and can shift to a Tc1 phenotype. Accordingly, Tc17 cells are endowed with a higher mitochondrial spare respiratory capacity than Tc1 cells and express higher levels of memory-related molecules than Tc1 cells. Together, these results demonstrate that in vitro-generated Tc17 cells acquire a central memory program and provide a lasting reservoir of Tc1 cells in vivo, thus supporting the use of Tc17 lymphocytes in the design of novel and more effective therapies

Morphological, immunological and biochemical characterization of purified transverse tubule membranes isolated from rabbit skeletal muscle

A microsomal fraction consisting of membranes of transverse tubule origin has been purified by a modification of the calcium-loading procedure initially described by Rosemblatt et al. (J Biol Chem 256:8140-8, 1981). Enzymatic analysis of this fraction shows an enrichment of the vesicles in the Mg++ATPase (basal) activity characteristic of the T-tubules and an absent or very low Ca++-dependant ATPase activity. Stereological analysis of freeze fracture replica of the membranes in the purified fraction indicates that they have a very low density of particles in their P faces and lack the structural manifestation of the caveolae typical of the sarcolemma. Immunological analysis performed with monoclonal antibodies prepared against purified T-tubule and sarcoplasmic reticulum membranes define some T-tubule specific antigens and confirm the morphological and biochemical data regarding the origin and purity of the Ttubule preparation. © 1989 Kluwer Academic Publishers

Engendering the health agenda? Reflections on the Chilean case, 2000-2010

Despite a growing body of research on gender and social policy, little attention has been given to work on the health sector. Drawing on the Chilean case, this paper examines the opportunities and constraints for producing positive gender outcomes in health policy. The paper argues that only limited progress has been made in integrating gender issues into the health sector despite several entry points introduced over the past decade. Part of the explanation lies in the continuing dominance of economic technocrats in the design of health sector reform. Even where attention is given to gender within the health sector, it has been narrowly defined, with a predominant focus on “equity” rather than “equality” issues and an on-going failure to acknowledge the contribution of the care economy in the majority of health reform debates. At the same time, relatively few women's organizations work on these issues and much of the work to broaden out notions of gender and health and push for change has fallen to a few key individuals. The Chilean political context has also limited the possibility for pushing for change within the health sector despite progress in other areas of social policy