Retinoic acid as a modulator of T cell immunity

Indexación: Scopus. DOAJ.Vitamin A, a generic designation for an array of organic molecules that includes retinal, retinol and retinoic acid, is an essential nutrient needed in a wide array of aspects including the proper functioning of the visual system, maintenance of cell function and differentiation, epithelial surface integrity, erythrocyte production, reproduction, and normal immune function. Vitamin A deficiency is one of the most common micronutrient deficiencies worldwide and is associated with defects in adaptive immunity. Reports from epidemiological studies, clinical trials and experimental studies have clearly demonstrated that vitamin A plays a central role in immunity and that its deficiency is the cause of broad immune alterations including decreased humoral and cellular responses, inadequate immune regulation, weak response to vaccines and poor lymphoid organ development. In this review, we will examine the role of vitamin A in immunity and focus on several aspects of T cell biology such as T helper cell differentiation, function and homing, as well as lymphoid organ development. Further, we will provide an overview of the effects of vitamin A deficiency in the adaptive immune responses and how retinoic acid, through its effect on T cells can fine-tune the balance between tolerance and immunity.http://www.mdpi.com/2072-6643/8/6/34

[Translation] Aquele evento, esta memória: notas sobre a antropologia das diásporas africanas no Novo Mundo

Translation by Rogerio Brittes W. Pires and Julia Sauma of: Scott, David (1991). "That Event, This Memory: Notes on the Anthropology of African Diasporas in the New World." Diaspora: A Journal of Transnational Studies, vol. 1 no. 3, p. 261-284: Resumo: Neste artigo de 1991, David Scott analisa importantes marcos da antropologia estadunidense acerca dos povos de ascendência africana no Novo Mundo: o trabalho de Melville Herskovits, nos anos 1920 a 1940, e o de Richard Price, nos anos 1970 e 1980 – dando ênfase às pesquisas de ambos entre os Saamaka do Suriname, que figuram como “uma espécie de metonímia antropológica” nas discussões sobre a diáspora africana nas Américas. Scott buscará compreender como a “ciência da cultura” fundada por Boas construiu “o Negro do Novo Mundo” como objeto teórico e passou a fornecer o vocabulário autorizado capaz de identificá-lo e de representá-lo. O autor tece críticas ao modo como tal antropologia constrói uma narrativa de continuidades entre memórias precisas no presente e os tropos “África” e “escravidão” em passados autênticos e verificáveis, para depois propor aquelas que considera serem as tarefas teóricas adequadas para o complexo campo discursivo da “tradição”

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

Cyclophilin C-associated protein (CyCAP) knock-out mice spontaneously develop colonic mucosal hyperplasia and exaggerated tumorigenesis after treatment with carcinogen azoxymethane1

<p>Abstract</p> <p>Background</p> <p>The discovery of a "serrated neoplasia pathway" has highlighted the role of hyperplastic lesions of the colon as the significant precursor of colorectal adenocarcinoma. In mice, hyperplasia of the colonic mucosa is a regular phenomenon after a challenge with colonic carcinogens indicating that mucosal hyperproliferation and thickening, even without cytological dysplasia, represents an early pre-malignant change. Cyclophilin C-associated protein (CyCAP) has been described to down-modulate endotoxin signaling in colorectal murine mucosa and is a murine orthologue of the tumor-associated antigen 90 K (TAA90K)/mac-2-binding protein.</p> <p>Methods</p> <p>Female Balb/c wild-type (WT) and CyCAP knock-out (KO) mice (6–8 weeks old) were administered 2 or 6 weekly subcutaneous injections of azoxymethane. The animals were evaluated post-injection at six weeks for aberrant crypt foci (ACF) study and at five months for colon tumor measurement. The thickness of the colon crypts was measured in microns and the number of colonocytes per crypt was also determined in well-oriented crypts. Morphometric analyses of the colon mucosa were also performed in untreated 6–8 weeks old KO and WT animals. Formalin-fixed/paraffin-embedded colon sections were also studied by immunohistochemistry to determine the Ki-67 proliferation fraction of the colon mucosa, β-catenin cellular localization, cyclin D1, c-myc, and lysozyme in Paneth cells.</p> <p>Results</p> <p>Cyclophilin C-associated protein (CyCAP)^-/-mice, spontaneously developed colonic mucosal hyperplasia early in life compared to wild-type mice (WT) (p < 0.0001, T-test) and crypts of colonic mucosa of the (CyCAP)^-/-mice show higher proliferation rate (p = 0.039, Mann-Whitney Test) and larger number of cyclin D1-positive cells (p < 0.0001, Mann-Whitney Test). Proliferation fraction and cyclin D1 expression showed positive linear association (p = 0.019, Linear-by-Linear Association). The hyperplasia was even more pronounced in CyCAP^-/-mice than in WT after challenge with azoxymethane (p = 0.005, T-test). The length of the crypts (r = 0.723, p = 0.018, Spearman Correlation) and the number of colonocytes per crypt (r = 0.863, p = 0.001, Spearman Correlation) in non-tumorous areas were positively associated with azoxymethane-induced number of tumors. CyCAP^-/-developed larger numbers of tumors than WT animals (p = 0.003, T-Test) as well as overall larger tumor mass (p = 0.016, T-Test). Membranous β-catenin was focally overexpressed in KO mice including proliferative zone of the crypts.</p> <p>Conclusion</p> <p>CyCAP^-/-represent the first described model of spontaneous colonic mucosal hyperplasia. We conclude that CyCAP-deficient mice spontaneously and after challenge with carcinogen develop significantly more colorectal mucosal hyperplasia, an early stage in murine colonic carcinogenesis.</p

Quality of life in spondyloarthritis : analysis of a large Brazilian cohort

Objetivo: analisar as variáveis demográficas e clínicas associadas à diminuição da qualidade de vida em uma grande coorte brasileira de pacientes com espondiloartrite (EpA). Métodos: Foi aplicado um protocolo de pesquisa único a 1.465 pacientes brasileiros classificados como tendo EpA de acordo com os critérios do European Spondyloarthropaties Study Group (ESSG), atendidos em 29 centros de referência em reumatologia do Brasil. Foram registradas as variáveis clínicas e demográficas. A qualidade de vida foi analisada por meio do questionário Ankylosing Spondylitis Quality of Life (ASQoL). Resultados: A pontuação média do ASQoL foi de 7,74 (+ 5,39). Ao analisar doenças específicas no grupo de EpA, as pontuações do ASQoL não apresentaram diferença estatisticamente significativa. Os dados demográficos mostraram piores escores de ASQoL associados ao gênero feminino (p = 0,014) e etnia negra (p < 0,001). Quanto aos sintomas clínicos, a dor na região glútea (p = 0,032), a dor cervical (p < 0,001) e a dor no quadril (p = 0,001), estiveram estatisticamente associadas a piores escores no ASQoL. O uso contínuo de fármacos anti-inflamatórios não esteroides (p < 0,001) e agentes biológicos (p = 0,044) esteve associado a escores mais elevados de ASQoL, enquanto outros medicamentos não interferiram nos escores do ASQoL. Conclusão: Nesta grande série de pacientes com EpA, o sexo feminino e a etnia negra, bem como sintomas predominantemente axiais, estiveram associados a uma qualidade de vida reduzida.Objective: to analyze quality of life and demographic and clinical variables associated to its impairment in a large Brazilian cohort of patients with spondyloarthritis (SpA). Methods: A common protocol of investigation was applied to 1465 Brazilian patients classified as SpA according to the European Spondyloarthropaties Study Group (ESSG) criteria, attended at 29 reference centers for Rheumatology in Brazil. Clinical and demographic variables were recorded. Quality of life was analyzed through the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. Results: The mean ASQoL score was 7.74 (± 5.39). When analyzing the specific diseases in the SpA group, the ASQoL scores did not present statistical significance. Demographic data showed worse scores of ASQoL associated with female gender (p = 0.014) and African-Brazilian ethnicity (p < 0.001). Regarding clinical symptoms, buttock pain (p = 0.032), cervical pain (p < 0.001) and hip pain (p = 0.001), were statistically associated with worse scores of ASQoL. Continuous use of nonsteroidal anti-inflammatory drugs (p < 0.001) and biologic agents (p = 0.044) were associated with higher scores of ASQoL, while the other medications did not interfere with the ASQoL scores. Conclusion: In this large series of patients with SpA, female gender and African-Brazilian ethnicity, as well as predominant axial symptoms, were associated with impaired quality of life