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Foxp3 flexibility

Nobuyuki Onai, Jumpei Asano, Rumiko Kurosaki, Shoko Kuroda, Toshiaki Ohteki
The basic helix-loop-helix transcription factor E2-2 is essential for the development of plasmacytoid dendritic cells (pDCs) but not conventional DCs (cDCs). Here, we generated E2-2 reporter mice and demonstrated that an E2-2high fraction among common DC progenitors, which are a major source of pDCs and cDCs in the steady state, strictly gave rise to pDCs in the presence of Flt3 (Fms-like tyrosine kinase receptor-3) ligand ex vivo or in the secondary lymphoid organs when transferred in vivo. However, in the small intestine, some of these E2-2high progenitors differentiated into cDCs that produced retinoic acid...
December 18, 2017: International Immunology
Megan E Muroski, Jason Miska, Alan L Chang, Peng Zhang, Aida Rashidi, Haley Moore, Aurora Lopez-Rosas, Yu Han, Maciej S Lesniak
Fatty acid (FA) metabolism directly influences the functional capabilities of T cells in tumor microenvironments. Thus, developing tools to interrogate FA-uptake by T cell subsets is important for understanding tumor immunosuppression. Herein, we have generated a novel FA-Qdot 605 dye conjugate with superior sensitivity and flexibility to any of the previously commercially available alternatives. For the first time, we demonstrate that this nanoparticle can be used as a specific measure of fatty acid uptake by T cells both in-vitro and in-vivo...
July 19, 2017: Scientific Reports
Duncheng Wang, Debjani Ghosh, S M Touhidul Islam, Cody D Moorman, Ashton E Thomason, Daniel S Wilkinson, Mark D Mannie
This study introduces a flexible format for tolerogenic vaccination that incorporates IFN-β and neuroantigen (NAg) in the Alum adjuvant. Tolerogenic vaccination required all three components, IFN-β, NAg, and Alum, for inhibition of experimental autoimmune encephalomyelitis (EAE) and induction of tolerance. Vaccination with IFN-β + NAg in Alum ameliorated NAg-specific sensitization and inhibited EAE in C57BL/6 mice in pretreatment and therapeutic regimens. Tolerance induction was specific for the tolerogenic vaccine Ag PLP178-191 or myelin oligodendrocyte glycoprotein (MOG)35-55 in proteolipid protein- and MOG-induced models of EAE, respectively, and was abrogated by pretreatment with a depleting anti-CD25 mAb...
October 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Jose M Rojo, Gloria Ojeda, Yenny Y Acosta, Maria Montes-Casado, Gabriel Criado, Pilar Portolés
Tregs are anergic CD4(+)CD25(+)Foxp3(+) T lymphocytes exerting active suppression to control immune and autoimmune responses. However, the factors in TCR recognition underlying Treg differentiation are unclear. Based on our previous data, we hypothesized that Treg TCR/CD3 antigen receptor complexes might differ from those of CD4(+)CD25(-) Tconv. Expression levels of TCR/CD3, CD3ε,ζ chains, or other molecules involved in antigen signaling and the characteristics of CD3ε chains were analyzed in thymus or spleen Treg cells from normal mice...
March 2014: Journal of Leukocyte Biology
Calvin Wei, Sasis Sirikanjanapong, Seth Lieberman, Mark Delacure, Frank Martiniuk, William Levis, Beverly Y Wang
Primary malignant melanoma arising from the eustachian tube is extremely rare. We report the case of a 63-year-old white man who presented with a 1-month history of left-sided hearing loss and aural fullness. Flexible fiberoptic laryngoscopy detected a blue-purple mass that appeared to arise from the left lateral nasopharynx. Computed tomography demonstrated an enhancing mass arising from an orifice of the left eustachian tube. The tumor was debulked endoscopically and was confirmed to have originated in the left eustachian tube...
January 2013: Ear, Nose, & Throat Journal
Kenneth J Oestreich, Amy S Weinmann
There is an emerging body of research demonstrating that the co-expression of key lineage-specifying transcription factors, commonly referred to as 'master regulators', affects the functional capabilities and flexibility of CD4(+) T cell subsets. Here, we discuss how the natural co-expression of these lineage-specifying transcription factors has challenged the concept that the expression of a single 'master regulator' strictly establishes an absolute CD4(+) T cell phenotype. Instead, it is becoming clear that the interplay between the lineage-specifying (or lineage-defining) transcription factors, including T-bet, GATA3, RORγt, BCL-6 and FOXP3, contributes to the fate and flexibility of CD4(+) T cell subtypes...
2012: Nature Reviews. Immunology
James B Wing, Shimon Sakaguchi
Foxp3(+) regulatory T cells (Tregs) are a constitutively immunosuppressive cell type critical for the control of autoimmunity and inflammatory pathology. A range of mechanisms of Treg suppression have been identified and it has not always been clear how these different mechanisms interact in order to properly suppress autoimmunity and excessive inflammation. In recent years it has become clear that, while all Tregs seem to share some core suppressive mechanisms, they are also able to adapt to their surroundings in response to a variety of stimuli by homing to the sites of inflammation and exerting ancillary suppressive functions...
2012: Frontiers in Immunology
Kalina Świst, Elżbieta Pajtasz-Piasecka
A number of distinguished populations with manifold functions and various pathways of differentiation have been identified within T lymphocytes. The cells expressing CD4 coreceptor on their cell surface are the most varied group. Depending on changes in different tissue microenvironments induced by such cytokines as IL-4, IFN-γ, IL-10 or TGF-β, CD4+ T lymphocytes can differentiate into alternative subpopulations performing helper, regulatory/suppressor function (Th1, Th2, Th9, Th17, Th22, Tfh, iTreg and Tr1)...
2011: Postȩpy Higieny i Medycyny Doświadczalnej
R A O'Connor, L S Taams, S M Anderton
CD4(+) T cells display considerable flexibility in their effector functions, allowing them to tackle most effectively the range of pathogenic infections with which we are challenged. The classical T helper (Th) 1 and Th2 subsets have been joined recently by the Th17 lineage. If not controlled, the potent effector functions (chiefly cytokine production) of which these different cells are capable can lead to (sometimes fatal) autoimmune and allergic inflammation. The primary cell population tasked with providing this control appears to be CD4(+) regulatory T (T(reg)) cells expressing the forkhead box P3 (FoxP3) transcription factor...
February 2010: Clinical and Experimental Immunology
Liang Zhou, Mark M W Chong, Dan R Littman
The differentiation of naive CD4(+) T cells into lineages with distinct effector functions has been considered to be an irreversible event. T helper type 1 (Th1) cells stably express IFN-gamma, whereas Th2 cells express IL-4. The discovery and investigation of two other CD4(+) T cell subsets, induced regulatory T (iTreg) cells and Th17 cells, has led to a rethinking of the notion that helper T cell subsets represent irreversibly differentiated endpoints. Accumulating evidence suggests that CD4(+) T cells, particularly iTreg and Th17 cells, are more plastic than previously appreciated...
May 2009: Immunity
Noriko Komatsu, Maria Encarnita Mariotti-Ferrandiz, Ying Wang, Bernard Malissen, Herman Waldmann, Shohei Hori
Natural regulatory T cells (T(reg)) represent a distinct lineage of T lymphocytes committed to suppressive functions, and expression of the transcription factor Foxp3 is thought to identify this lineage specifically. Here we report that, whereas the majority of natural CD4(+)Foxp3(+) T cells maintain stable Foxp3 expression after adoptive transfer to lymphopenic or lymphoreplete recipients, a minor fraction enriched within the CD25(-) subset actually lose it. Some of those Foxp3(-) T cells adopt effector helper T cell (T(h)) functions, whereas some retain "memory" of previous Foxp3 expression, reacquiring Foxp3 upon activation...
February 10, 2009: Proceedings of the National Academy of Sciences of the United States of America
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