collection
https://read.qxmd.com/read/22520844/the-jak-stat-pathway-at-twenty
#1
REVIEW
George R Stark, James E Darnell
We look back on the discoveries that the tyrosine kinases TYK2 and JAK1 and the transcription factors STAT1, STAT2, and IRF9 are required for the cellular response to type I interferons. This initial description of the JAK-STAT pathway led quickly to additional discoveries that type II interferons and many other cytokines signal through similar mechanisms. This well-understood pathway now serves as a paradigm showing how information from protein-protein contacts at the cell surface can be conveyed directly to genes in the nucleus...
April 20, 2012: Immunity
https://read.qxmd.com/read/26116499/cd4-t-cell-depletion-substantially-augments-the-rescue-potential-of-pd-l1-blockade-for-deeply-exhausted-cd8-t-cells
#2
JOURNAL ARTICLE
Pablo Penaloza-MacMaster, Nicholas M Provine, Eryn Blass, Dan H Barouch
In various models of chronic infections and cancers, blockade of the inhibitory programmed cell death-1 (PD-1) pathway has been shown to be promising at restoring immune function. However, there is not a complete understanding of the factors that influence responsiveness to programmed death-ligand 1 (PD-L1) blockade. In particular, it is currently unclear whether the efficacy of PD-L1 blockade is dependent on the stage of disease. In a model of chronic lymphocytic choriomeningitis virus infection in mice, we show that exhausted CD8 T cells during the late stage of infection are refractory to rescue by PD-L1 blockade...
August 1, 2015: Journal of Immunology
https://read.qxmd.com/read/25976514/t-cell-responses-b-cells-control-t-cell-traffic
#3
COMMENT
Elisabeth Kugelberg
No abstract text is available yet for this article.
June 2015: Nature Reviews. Immunology
https://read.qxmd.com/read/26085205/ubiquitin-dependent-regulation-of-foxp3-and-treg-function
#4
REVIEW
Joseph Barbi, Drew M Pardoll, Fan Pan
Regulatory T (Treg) cells are crucial enforcers of immune homeostasis. Their characteristic suppressive function largely arises from an equally unique pattern of gene expression. A complex network of factors and processes contribute to this 'signature' Treg gene expression landscape. Many of these alter the level and activity of the Treg-defining transcription factor Foxp3. As stable expression of Foxp3 is important for the ability of Treg cells to successfully prevent excessive or inappropriate immune activation, uncovering the mechanisms regulating Foxp3 level is required for the understanding and therapeutic exploitation of Tregs...
July 2015: Immunological Reviews
https://read.qxmd.com/read/25477212/t-cell-immunity-functional-heterogeneity-of-human-memory-cd4%C3%A2-%C2%BA-t-cell-clones-primed-by-pathogens-or-vaccines
#5
JOURNAL ARTICLE
Simone Becattini, Daniela Latorre, Federico Mele, Mathilde Foglierini, Corinne De Gregorio, Antonino Cassotta, Blanca Fernandez, Sander Kelderman, Ton N Schumacher, Davide Corti, Antonio Lanzavecchia, Federica Sallusto
Distinct types of CD4(+) T cells protect the host against different classes of pathogens. However, it is unclear whether a given pathogen induces a single type of polarized T cell. By combining antigenic stimulation and T cell receptor deep sequencing, we found that human pathogen- and vaccine-specific T helper 1 (T(H)1), T(H)2, and T(H)17 memory cells have different frequencies but comparable diversity and comprise not only clones polarized toward a single fate, but also clones whose progeny have acquired multiple fates...
January 23, 2015: Science
https://read.qxmd.com/read/26078274/the-mapk-activated-kinase-mk2-attenuates-dendritic-cell-mediated-th1-differentiation-and-autoimmune-encephalomyelitis
#6
JOURNAL ARTICLE
Klara Soukup, Angela Halfmann, Marie Le Bras, Emine Sahin, Sarah Vittori, Fiona Poyer, Cornelia Schuh, Romana Luger, Birgit Niederreiter, Thomas Haider, Dagmar Stoiber, Stephan Blüml, Gernot Schabbauer, Alexey Kotlyarov, Matthias Gaestel, Thomas Felzmann, Alexander M Dohnal
Dendritic cell (DC)-mediated inflammation induced via TLRs is promoted by MAPK-activated protein kinase (MK)-2, a substrate of p38 MAPK. In this study we show an opposing role of MK2, by which it consolidates immune regulatory functions in DCs through modulation of p38, ERK1/2-MAPK, and STAT3 signaling. During primary TLR/p38 signaling, MK2 mediates the inhibition of p38 activation and positively cross-regulates ERK1/2 activity, leading to a reduction of IL-12 and IL-1α/β secretion. Consequently, MK2 impairs secondary autocrine IL-1α signaling in DCs, which further decreases the IL-1α/p38 but increases the anti-inflammatory IL-10/STAT3 signaling route...
July 15, 2015: Journal of Immunology
https://read.qxmd.com/read/25882245/the-promise-of-low-dose-interleukin-2-therapy-for-autoimmune-and-inflammatory-diseases
#7
REVIEW
David Klatzmann, Abul K Abbas
Depletion of regulatory T (TReg) cells in otherwise healthy individuals leads to multi-organ autoimmune disease and inflammation. This indicates that in a normal immune system, there are self-specific effector T cells that are ready to attack normal tissue if they are not restrained by TReg cells. The data imply that there is a balance between effector T cells and TReg cells in health and suggest a therapeutic potential of TReg cells in diseases in which this balance is altered. Proof-of-concept clinical trials, now supported by robust mechanistic studies, have shown that low-dose interleukin-2 specifically expands and activates TReg cell populations and thus can control autoimmune diseases and inflammation...
May 2015: Nature Reviews. Immunology
https://read.qxmd.com/read/25665078/the-varieties-of-immunological-experience-of-pathogens-stress-and-dendritic-cells
#8
REVIEW
Bali Pulendran
In the 40 years since their discovery, dendritic cells (DCs) have been recognized as central players in immune regulation. DCs sense microbial stimuli through pathogen-recognition receptors (PRRs) and decode, integrate, and present information derived from such stimuli to T cells, thus stimulating immune responses. DCs can also regulate the quality of immune responses. Several functionally specialized subsets of DCs exist, but DCs also display functional plasticity in response to diverse stimuli. In addition to sensing pathogens via PRRs, emerging evidence suggests that DCs can also sense stress signals, such as amino acid starvation, through ancient stress and nutrient sensing pathways, to stimulate adaptive immunity...
2015: Annual Review of Immunology
https://read.qxmd.com/read/25665079/transcriptional-regulation-of-innate-and-adaptive-lymphocyte-lineages
#9
REVIEW
Maria Elena De Obaldia, Avinash Bhandoola
The lymphocyte family has expanded significantly in recent years to include not only the adaptive lymphocytes (T cells, B cells) and NK cells, but also several additional innate lymphoid cell (ILC) types. ILCs lack clonally distributed antigen receptors characteristic of adaptive lymphocytes and instead respond exclusively to signaling via germline-encoded receptors. ILCs resemble T cells more closely than any other leukocyte lineage at the transcriptome level and express many elements of the core T cell transcriptional program, including Notch, Gata3, Tcf7, and Bcl11b...
2015: Annual Review of Immunology
https://read.qxmd.com/read/25998961/lymph-node-fibroblastic-reticular-cells-in-health-and-disease
#10
REVIEW
Anne L Fletcher, Sophie E Acton, Konstantin Knoblich
Over the past decade, a series of discoveries relating to fibroblastic reticular cells (FRCs) — immunologically specialized myofibroblasts found in lymphoid tissue — has promoted these cells from benign bystanders to major players in the immune response. In this Review, we focus on recent advances regarding the immunobiology of lymph node-derived FRCs, presenting an updated view of crucial checkpoints during their development and their dynamic control of lymph node expansion and contraction during infection...
June 2015: Nature Reviews. Immunology
https://read.qxmd.com/read/25998963/perforin-and-granzymes-function-dysfunction-and-human-pathology
#11
REVIEW
Ilia Voskoboinik, James C Whisstock, Joseph A Trapani
A defining property of cytotoxic lymphocytes is their expression and regulated secretion of potent toxins, including the pore-forming protein perforin and serine protease granzymes. Until recently, mechanisms of pore formation and granzyme transfer into the target cell were poorly understood, but advances in structural and cellular biology have now begun to unravel how synergy between perforin and granzymes brings about target cell death. These and other advances are demonstrating the surprisingly broad pathophysiological roles of the perforin–granzyme pathway, and this has important implications for understanding immune homeostasis and for developing immunotherapies for cancer and other diseases...
June 2015: Nature Reviews. Immunology
https://read.qxmd.com/read/25706098/interleukin-22-immunobiology-and-pathology
#12
REVIEW
Jarrod A Dudakov, Alan M Hanash, Marcel R M van den Brink
Interleukin-22 (IL-22) is a recently described IL-10 family cytokine that is produced by T helper (Th) 17 cells, γδ T cells, NKT cells, and newly described innate lymphoid cells (ILCs). Knowledge of IL-22 biology has evolved rapidly since its discovery in 2000, and a role for IL-22 has been identified in numerous tissues, including the intestines, lung, liver, kidney, thymus, pancreas, and skin. IL-22 primarily targets nonhematopoietic epithelial and stromal cells, where it can promote proliferation and play a role in tissue regeneration...
2015: Annual Review of Immunology
https://read.qxmd.com/read/26084021/interleukin-33-in-tissue-homeostasis-injury-and-inflammation
#13
REVIEW
Ari B Molofsky, Adam K Savage, Richard M Locksley
Interleukin-33 (IL-33) is a nuclear-associated cytokine of the IL-1 family originally described as a potent inducer of allergic type 2 immunity. IL-33 signals via the receptor ST2, which is highly expressed on group 2 innate lymphoid cells (ILC2s) and T helper 2 (Th2) cells, thus underpinning its association with helminth infection and allergic pathology. Recent studies have revealed ST2 expression on subsets of regulatory T cells, and for a role for IL-33 in tissue homeostasis and repair that suggests previously unrecognized interactions within these cellular networks...
June 16, 2015: Immunity
https://read.qxmd.com/read/26085681/regulatory-rebound-in-il-12-treated-tumors-is-driven-by-uncommitted-peripheral-regulatory-t-cells
#14
JOURNAL ARTICLE
Qingsheng Li, Lauren P Virtuoso, Charles D Anderson, Nejat K Egilmez
IL-12 promotes a rapid reversal of immune suppression in the tumor microenvironment. However, the adjuvant activity of IL-12 is short-lived due to regulatory T cell (Treg) reinfiltration. Quantitative analysis of Treg kinetics in IL-12-treated tumors and tumor-draining lymph nodes revealed a transient loss followed by a rapid 4-fold expansion of tumor Treg between days 3 and 10. Subset-specific analysis demonstrated that the posttreatment rebound was driven by the CD4(+)CD25(+)Foxp3(+) neuropilin-1(low) peripheral Treg (pTreg), resulting in a 3-5-fold increase in the pTreg to CD4(+)CD25(+)Foxp3(+) neuropilin-1(high) thymic Treg ratio by day 10...
August 1, 2015: Journal of Immunology
https://read.qxmd.com/read/25263123/continuous-requirement-for-the-tcr-in-regulatory-t-cell-function
#15
JOURNAL ARTICLE
Andrew G Levine, Aaron Arvey, Wei Jin, Alexander Y Rudensky
Foxp3(+) regulatory T cells (T(reg) cells) maintain immunological tolerance, and their deficiency results in fatal multiorgan autoimmunity. Although heightened signaling via the T cell antigen receptor (TCR) is critical for the differentiation of T(reg) cells, the role of TCR signaling in T(reg) cell function remains largely unknown. Here we demonstrated that inducible ablation of the TCR resulted in T(reg) cell dysfunction that could not be attributed to impaired expression of the transcription factor Foxp3, decreased expression of T(reg) cell signature genes or altered ability to sense and consume interleukin 2 (IL-2)...
November 2014: Nature Immunology
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