JCI online ahead of print table of contents for June 2, 2014

Mucin concentration contributes to a sticky situation in cystic fibrosis

Patients with cystic fibrosis (CF) accumulate thick, sticky mucus in the lungs that clogs the airways and leads to life-threatening lung infections. It has recently been proposed that differing concentrations of mucin with in mucus layers of the CF lung contribute to decreased mucus clearance; however, it has been challenging to accurately access mucin concentration. In this issue of the Journal of Clinical Investigation, Mehmet Kesimer and colleagues at the University of North Carolina applied size exclusion chromatography/differential refractometry techniques to measure the mucin concentration in sputum from normal and CF airways. Mucin concentrations and partial osmotic pressure were greater in CF secretions compared to normal secretions. Importantly, increased mucin concentration and partial osmotic pressure promoted mucus stasis, thereby contributing to lung infection and inflammation in CF.

TITLE: Cystic fibrosis airway secretions exhibit mucin hyperconcentration and increased osmotic pressure

AUTHOR CONTACT: Mehmet Kesimer

The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Phone: 9198432577; E-mail: mehmet_kesimer@med.unc.edu

View this article at: http://www.jci.org/articles/view/73469

Engineered aptimer targets malignant and tumor-associated T cells

The transcription factor STAT3 mediates tumor survival, proliferation, invasion, and immunosuppression, and is persistently activated in tumor cells and tumor-associated immune cells. In T cells, STAT3 activation impairs anti-tumor responses, while inhibition or loss of STAT3 promotes anti-tumor responses. In this issue of the Journal of Clinical Investigation, Hua Yu and colleagues at the Beckman Research Institute developed an aptamer-based strategy to deliver STAT3 siRNA and inhibit STAT3 in tumor cells and tumor-associated immune cells. An aptamer that binds the cell surface receptor cytotoxic T lymphocyte-associated antigen-4 (CTLA), an inhibitor of the T cell anti-tumor response, was attached to STAT3 siRNA (CTLA4apt-STAT3 siRNA), allowing for targeted delivery to tumor-associated T cells, Tregs or malignant T cells. Local or systemic administration of CTLA4apt STAT3 siRNA in different murine tumor models decreased STAT3 expression in CTLA4-expressing T cells, reduced tumor-associated Tregs, and decreased tumor growth and metastasis. Importantly, CTLA4apt STAT3 siRNA inhibited tumor growth and promoted tumor cell apoptosis in mice bearing human T cell lymphoma.

TITLE: CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells

AUTHOR CONTACT: Hua Yu

Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

Phone: 626-471-7238; Fax: 626-256-8708; E-mail: hyu@coh.org

View this article at: http://www.jci.org/articles/view/73174

ALSO IN THIS ISSUE:

BONE BIOLOGY

TITLE: NOTCH inhibits osteoblast formation in inflammatory arthritis via noncanonical NF-κB

AUTHOR CONTACT: Lianping Xing

University of Rochester Medical Center, Rochester, NY, USA

Phone: 585.273.4090; Fax: 585.756.4468; E-mail: Lianping_xing@urmc.rochester.edu.

View this article at: http://www.jci.org/articles/view/68901

GASTROENTEROLOGY

TITLE: Myosin Vb uncoupling from RAB8A and RAB11A elicits microvillus inclusion disease

AUTHOR CONTACT: James Goldenring

Vanderbilt University School of Medicine, Nashville, TN, USA

Phone: 615-936-3726; Fax: 615-343-1591; E-mail: jim.goldenring@vanderbilt.edu

Or

Mitchell Shub

University of Arizona College of Medicine, Phoenix, AZ, USA

Phone: 602.933.0940; Fax: 602.933.0373; E-mail: mshub@phoenixchildrens.com.

View this article at: http://www.jci.org/articles/view/71651

HEPATOLOGY

Biliary repair and carcinogenesis are mediated by IL-33–dependent cholangiocyte proliferation

AUTHOR CONTACT: Jorge Bezerra

Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA

Phone: 5136363008; Fax: 5136365581; E-mail: jorge.bezerra@cchmc.org

View this article at: http://www.jci.org/articles/view/73742

HIV/AIDS

TITLE: Abnormal B cell memory subsets dominate HIV-specific responses in infected individuals

AUTHOR CONTACT: Susan Moir

National Institutes of Health, Bethesda, MD, USA

Phone: 301-402-4559; Fax: 301-480-0643; E-mail: smoir@niaid.nih.gov

View this article at: http://www.jci.org/articles/view/74351?key=97bbd7f61e344de76f06

Provided by Journal of Clinical Investigation