By Faith Uwadiae
Edited by William Branchett
Recently we welcomed Professor Phillip Ashton-Rickardt for an insightful lecture and journal club discussion on his latest science paper, describing the identification of a novel protein important for T cell proliferation. (Read the full article here: https://www.sciencemag.org/content/348/6238/995.full)
Effective CD8+ T cells responses are required for robust control of viral infections. However, during chronic infections, including clone 13 lymphocytic choriomenigitis virus (LCMV Cl13), the CD8+ T cell response becomes exhausted resulting in viral persistence. Ashton-Rickardt and colleagues used a forward genetic chemical mutagenesis approach to generate a panel of mouse lines, which they screened for enhanced CD8+ T cell responses during LCMV Cl13 infection.
Written by Judith Secklehner
Edited by Faith Uwadiae
In our latest Journal Club session we discussed a recent publication in the Journal of Immunology. Narumi et al. investigated the role of S100A8/A9 (or Calprotectin) in a tumor environment and discovered a new role of this protein for NK cell activation via interaction with RAGE (receptor of advanced glycation end product).
The study focused on the heterodimeric protein calprotectin, which is formed of the two Ca2+-binding proteins S100A8 and S100A9. Calprotectin can be found in the cytosol of myeloid cells, but not in lymphocytes. Many intracellular and extracellular proinflammatory functions are attributed to calprotectin, essentially regulation of leukocyte adhesion and migration and promotion of cytokine production.
Written by Caroline Anderson
Edited by John MacKey
The focus of our journal club this week was a recent paper from Science describing a novel mechanism by which neutrophils deposit chemokine-enriched way-markers to guide CD8+ T cells to the airways during influenza virus infection. (read the full article here http://www.sciencemag.org/content/349/6252/aaa4352.full).
Whilst the role of chemokines in attracting effector immune cells to sites of immune insult is well established, how localized chemokine gradients are produced and maintained is incompletely understood. Likewise, the molecular mechanisms linking neutrophils and T cell recruitment in viral infections is unclear. Lim et al therefore set out to investigate the hypothesis that neutrophils are responsible for generating chemokine gradients that guide influenza-specific CD8+ T cells in the airways.
Journal club with Gisli Jenkins from 21/9/15
Written by David Salman, Richard Toshner and Joana Alçada
Edited by Sarah Allden
We recently welcomed Dr Gisli Jenkins, Clinical Associate Professor & Reader in Pulmonary Biology from the University of Nottingham to the IRD Journal Club.
His recent publication “Influenza Promotes Collagen Deposition via αvβ6 Integrin-mediated Transforming Growth Factor β Activation” served as a starting point to discuss various aspects of research in lung fibrosis. The paper explores the relationship between influenza and idiopathic pulmonary fibrosis via transforming growth factor β (TGF-β), a cytokine involved in development, inflammation and wound repair.
The authors hypothesised that influenza-induced epithelial cell damage would stimulate toll-like receptor 3 (TLR3) activity, a receptor that recognizes by-products from viruses such as influenza.
Written by William Branchett
Edited by Judith Secklehner and Caroline Anderson
The immune system has a huge capacity for destruction which, if unrestrained, can cause collateral damage to host tissue. Immune responses must therefore have ‘off’ switches to limit their magnitude and avoid inflammatory disease. Conversely, pathogens and tumours can hijack these mechanisms of immune regulation to favour their own survival. Understanding of immune regulation may therefore allow the design of drugs to manipulate overly exuberant or insufficient immune responses.
Transforming growth factor β (TGF-β) is a multi-functional cytokine that can dampen immune responses, in part by suppressing the pro-inflammatory activity of effector CD4+ T cells (Teffs).