Epigenetic alterations disrupt intestinal T cell homeostasis
A precise balance between mature T cell subsets is important for intestinal homeostasis. Disruption of T cell populations underlies autoimmune colitis, including inflammatory bowel disease (IBD). Specific transcriptional programs are activated to determine the differentiation fate of naïve T cells; however, the role of epigenetic regulation in T cell maturation in the intestine is unclear. In this issue of the Journal of Clinical Investigation , Colby Zaph and colleagues from the University of British Columbia used a murine T cell transfer model, to demonstrate that T cell-specific expression of the histone lysine methyltransferase G9A is required for pathogenic T cell responses and colitis progression. G9A expression in naïve T cells prevented development of Th17 and Treg subsets and was associated with increased histone methylation. Pharmacologic inhibition of G9A restored the ability of T cells to differentiate into Treg and Th17 subsets, suggesting that targeting G9A may relieve intestinal inflammatory disease.
TITLE: Methyltransferase G9A regulates T cell differentiation during murine intestinal inflammation
AUTHOR CONTACT: Colby Zaph
The University of British Columbia, Vancouver, BC, CAN
Phone: 604-822-7231; Fax: 604-822-7815; E-mail: colby@brc.ubc.ca
View this article at: http://www.jci.org/articles/view/69592
Researchers develop a conditionally immortalized human β cell line
Pancreatic β cells maintain glucose homeostasis through storage and release of insulin. Diabetic patients exhibit drastic reduction and dysfunction in β cell populations, which cannot be regenerated or restored. Most of our current understanding of β cell mass regulation comes from experiments done with murine β cells; however, due to the limited availability of primary human β cells in depth analysis on these cells has been a challence. In this issue of the Journal of Clinical Investigation , Philippe Ravassard and colleagues at Hôpital Pitié Salpêtrière generated a conditionally immortalized human β cell line (EndoC-βH2) that can be greatly expanded before inducing excision of the immortalizing transgenes. Following excision, gene expression profiles of EndoC-βH2 cells were similar to isolated human pancreatic islets. Furthermore, excised EndoC-βH2 cells produced and stored insulin, which was released upon glucose stimulation. As representative human β cells, EndoC-βH2 cell provide a unique tool to further examine human-specific β cell properties and proliferation.
TITLE: Development of a conditionally immortalized human pancreatic β cell line
AUTHOR CONTACT: Philippe Ravassard
CRiICM UPMC / INSERM UMRS_975 / CNRS UMR7225, Paris, UNK, FRA
Phone: 33 1 57 27 45 75; E-mail: philippe.ravassard@upmc.fr
View this article at: http://www.jci.org/articles/view/72674
IMMUNOLOGY
TITLE: CaMK4-dependent activation of AKT/mTOR and CREM-α underlies autoimmunity-associated Th17 imbalance
AUTHOR CONTACT: George Tsokos
Beth Israel Deaconess Medical Center, Boston, MA, USA
Phone: 617-735 4160 (Betty Chase); E-mail: gtsokos@bidmc.harvard.edu
View this article at: http://www.jci.org/articles/view/73411
TITLE: PD-1 identifies the patient-specific CD8 + tumor-reactive repertoire infiltrating human tumors
AUTHOR CONTACT: Steven Rosenberg
National Institutes of Health, NIH, National Cancer Institute, Bethesda, MD, USA
Phone: 301-496-4164; E-mail: SAR@nih.gov
View this article at: http://www.jci.org/articles/view/73639
INFLAMMATION
TITLE: Sphingosine-1-phosphate receptor 1 reporter mice reveal receptor activation sites in vivo
AUTHOR CONTACT: Richard Proia
NIDDK/NIH, Bethesda, MD, USA
Phone: 301-435-6504; E-mail: richardP@intra.niddk.nih.gov
View this article at: http://www.jci.org/articles/view/71194
ONCOLOGY
TITLE: RIP140 increases APC expression and controls intestinal homeostasis and tumorigenesis
AUTHOR CONTACT: Vincent Cavailles
IRCM, Institut de Recherche en cancérologie de Montpellier, Montpellier, FRA
Phone: 33 4 67 61 24 05; E-mail: vincent.cavailles@inserm.fr
View this article at: http://www.jci.org/articles/view/65178
METABOLISM
TITLE: Leptin-promoted cilia assembly is critical for normal energy balance
AUTHOR CONTACT: Min-Seon Kim
Department of Internal Medicine University of Ulsan College of Medicine, Seoul, KOR
Phone: 82-2-3010-3245; E-mail: mskim@amc.seoul.kr
View this article at: http://www.jci.org/articles/view/69395
Journal of Clinical Investigation