1.
Stories From the Dendritic Cell Guardhouse.
Hoober, JK, Eggink, LL, Cote, R
Frontiers in immunology. 2019;:2880
Abstract
Phagocytic cells [dendritic cells (DCs), macrophages, monocytes, neutrophils, and mast cells] utilize C-type (Ca2+-dependent) lectin-like (CLEC) receptors to identify and internalize pathogens or danger signals. As monitors of environmental imbalances, CLEC receptors are particularly important in the function of DCs. Activation of the immune system requires, in sequence, presentation of antigen to the T cell receptor (TCR) by DCs, interaction of co-stimulatory factors such as CD40/80/86 on DCs with CD40L and CD28 on T cells, and production of IL-12 and/or IFN-α/β to amplify T cell differentiation and expansion. Without this sequence of events within an inflammatory environment, or in a different order, antigen-specific T cells become unresponsive, are deleted or become regulatory T cells. Thus, the mode by which CLEC receptors on DCs are engaged can either elicit activation of T cells to achieve an immune response or induce tolerance. This minireview illustrates these aspects with Dectin-1, DEC205, the mannose receptor and CLEC10A as examples.
2.
Dysfunctional Natural Killer Cells in the Aftermath of Cancer Surgery.
Angka, L, Khan, ST, Kilgour, MK, Xu, R, Kennedy, MA, Auer, RC
International journal of molecular sciences. 2017;(8)
Abstract
The physiological changes that occur immediately following cancer surgeries initiate a chain of events that ultimately result in a short pro-, followed by a prolonged anti-, inflammatory period. Natural Killer (NK) cells are severely affected during this period in the recovering cancer patient. NK cells play a crucial role in anti-tumour immunity because of their innate ability to differentiate between malignant versus normal cells. Therefore, an opportunity arises in the aftermath of cancer surgery for residual cancer cells, including distant metastases, to gain a foothold in the absence of NK cell surveillance. Here, we describe the post-operative environment and how the release of sympathetic stress-related factors (e.g., cortisol, prostaglandins, catecholamines), anti-inflammatory cytokines (e.g., IL-6, TGF-β), and myeloid derived suppressor cells, mediate NK cell dysfunction. A snapshot of current and recently completed clinical trials specifically addressing NK cell dysfunction post-surgery is also discussed. In collecting and summarizing results from these different aspects of the surgical stress response, a comprehensive view of the NK cell suppressive effects of surgery is presented. Peri-operative therapies to mitigate NK cell suppression in the post-operative period could improve curative outcomes following cancer surgery.
3.
Essentials of Th17 cell commitment and plasticity.
Muranski, P, Restifo, NP
Blood. 2013;(13):2402-14
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Abstract
CD4(+) T helper (Th) cells exist in a variety of epigenetic states that determine their function, phenotype, and capacity for persistence. These polarization states include Th1, Th2, Th17, and Foxp3(+) T regulatory cells, as well as the more recently described T follicular helper, Th9, and Th22 cells. Th17 cells express the master transcriptional regulator retinoic acid-related orphan receptor γ thymus and produce canonical interleukin (IL)-17A and IL-17F cytokines. Th17 cells display a great degree of context-dependent plasticity, as they are capable of acquiring functional characteristics of Th1 cells. This late plasticity may contribute to the protection against microbes, plays a role in the development of autoimmunity, and is necessary for antitumor activity of Th17 cells in adoptive cell transfer therapy models. Moreover, plasticity of this subset is associated with higher in vivo survival and self-renewal capacity and less senescence than Th1 polarized cells, which have less plasticity and more phenotypic stability. New findings indicate that subset polarization of CD4(+) T cells not only induces characteristic patterns of surface markers and cytokine production but also has a maturational aspect that affects a cell's ability to survive, respond to secondary stimulation, and form long-term immune memory.
4.
[Regulation of central tolerance by RANKL signaling].
Shinzawa, M, Akiyama, T
Clinical calcium. 2011;(8):1193-9
Abstract
RANKL (receptor activator of NF-κB ligand) is a member of TNF (tumor-necrosis factor) family cytokine. Several genetic studies indicated critical roles of RANKL and its receptor RANK in bone homeostasis. RANKL-RANK signal regulates differentiation, survival and activation of osteoclasts. Therefore, suppression of the RANKL signal would be a promising strategy for interventions in osteoporosis or rheumatoid arthritis. Indeed, humanized anti-RANKL neutralizing antibody is coming onto the market as an antiresorptive agent for osteoporosis treatment. In addition to the role on bone homeostasis, several studies suggested that the RANKL-RANK interaction regulates immune response and development. For instance, RANKL was previously identified as a survival factor for dendritic cells. Moreover, we and other groups reported that the RANKL signal contributes to development of medullary thymic epithelial cells (mTECs) . mTECs ectopically express and present a number of tissue restricted antigens (e.g. insulin) of which expressions are in part regulated by autoimmune regulator (Aire) , a factor responsible for a genetic human autoimmune disorder, thereby eliminating T cells reactive to these tissue restricted self-antigens. As result, RANKL is involved in establishment of self-tolerance in thymus by regulating the development of mTECs expressing Aire and tissue restricted antigens.