Regulatory T cells (Tregs) modulate the function of a variety of immune cells and are critical for maintaining self tolerance and preventing the development of autoimmune disease. Due to their ability to suppress effector T cells, Tregs have been increasingly explored for clinical use to suppress alloresponses. While this approach has been promising in preclinical models and early clinical trials, widespread clinical use of Tregs has been limited by the low number of these cells in the periphery and the unknown frequency of allo-responsive Tregs. In this issue of the
Matthias Edinger
Precise epigenetic modifications in stem cells control developmental programs and cell fate decisions. In particular, the addition or removal of trimethylation of histone 3 lysine 27 (H3K27me3) at lineage-specific genes has been linked to the repression of gene expression, and a precise balance of methyltransferases and demethylases within cells determines H3K27me3 levels. The demethylase UTX is essential for development and tissue homeostasis; however, a role for UTX in stem cell–mediated tissue regeneration is unknown. In this issue of the
Ling Liu, Thomas A. Rando
Male osteoporosis is a multifactorial disease, although it is often in part related to hypogonadism. While testosterone replacement therapy has been shown to improve bone mineral density, studies have also linked bone loss and higher fracture risk in men to low estrogen levels. In this issue of the
Thomas J. Weber
The central role of the transcriptional template of the hepatitis B virus (HBV), covalently closed circular DNA (cccDNA), has been difficult to study in patients with chronic hepatitis B (CHB) infection. In this issue of the
Peter A. Revill, Stephen A. Locarnini
Although the cognitive and biological characteristics of Alzheimer’s disease (AD) are well known and mouse models of AD are available, current treatments for AD-related cognitive deficits have quite limited efficacy. The development of tasks with cross-species validity may enable better prediction of the efficacy of potential new treatments. In this issue of the
Kerin K. Higa, Jared W. Young, Mark A. Geyer
Cancer immunotherapy in which cytotoxic T cells (CTLs) target tumor-specific antigens complexed to MHC-I molecules has been used successfully for several types of cancer; however, MHC-I is frequently downregulated in tumors, resulting in CTL evasion. Recently, it has been shown that MHC-Ilo tumors produce a set of T cell epitopes associated with impaired peptide processing (TEIPP) that have potential to be exploited for immunotherapy. TEIPP-specific CTLs recognize tumors defective in antigen presentation machinery (APM) but not those with intact APM. In this issue of the
Rolf Kiessling
Overexpression of FGF23 results in hypophosphatemic rickets, which is characterized by renal phosphate wasting, inappropriately low circulating levels of the active form of vitamin D, and skeletal abnormalities. The precise mechanisms of how excess FGF23 leads to hypophosphatemic rickets are not clear. In this issue of the
Valentin David, Myles Wolf
Circadian rhythms mediated by both central and tissue-specific peripheral clocks allow for the synchronization of biological processes with diurnal cycles such as activity and rest. Disruption of these rhythms can be caused by altered sleep-awake patterns or by pathological conditions and can initiate or exacerbate human disease through mechanisms that are only partially understood. In this issue, Dudek et al. identify a chondrocyte-autonomous cartilage clock and demonstrate that expression of an important circadian pacemaker, BMAL1, decreases during osteoarthritis progression. They show that chondrocyte-specific deletion of BMAL1 leads to cartilage degradation and disruption of key pathways, shifting cartilage homeostasis toward a catabolic state. These findings provide insight into the interplay between circadian rhythm and cartilage in osteoarthritis.
Karen M. Doody, Nunzio Bottini
The clinical application of T cell immunotherapy depends on ex vivo modification and expansion of T cells for adoptive transfer. In preclinical models, the use of a purified, naive T cell subset enhances persistence and antitumor immunity; however, the majority of clinical studies rely on modification of mixed populations of T cells that contain only a small subset of highly functional T cells with less-differentiated phenotype. In this month’s issue of the
Yang Xu, Gianpietro Dotti
The development of high-affinity antibodies in response to infection is an iterative process in which B cells cycle between proliferation/somatic hypermutation and antigen-driven selection. These processes occur within specific regions of the secondary lymphoid structures known as germinal centers (GCs) and the environmental and signaling cues provided by these regions guide the GC reactions that drive B cell maturation and antibody production, ultimately determining B cell fate. In this issue of the
Yee Ling Wu, Cristina Rada
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