Millet Treinin*

Department of Medical Neurobiology, Hadassah Medical School – Hebrew University, Jerusalem, Israel

The nicotinic acetylcholine receptor (nAChR) gene family encodes for subunits of acetylcholine gated ion channels. These receptors are expressed widely and have many functions including anti-inflammatory effects mediated by the α7 nAChR, as part of the cholinergic anti-inflammatory pathway, in immune cells, microglia and astrocytes. Maturation of α7 nAChRs into functional ligand-gated ion channels in the plasma membrane is a complex process likely to require the RIC-3 protein. This endoplasmic reticulum resident chaperone affects maturation of multiple nAChRs, but its interaction with these receptors and its effects on their maturation differ for different nAChRs. Moreover, these interactions and effects are regulated by multiple mechanisms. Genetic analysis has implicated RIC-3 in the neuroinflammatory disease Multiple Sclerosis (MS), and in the neurodegenerative Parkinson's disease (PD). Neuroinflammation contributes to the progression of neurodegenerative diseases including PD. This information combines to suggest that RIC-3 may contribute to progression of both MS and PD via its effects on the α7 nAChR and the cholinergic anti-inflammatory pathway. Furthermore, we suggest that mechanisms regulating RIC-3 expression and activity may have a role in controlling inflammation.

DOI: 10.29245/2578-3009/2018/1.1106 View / Download Pdf

Julie D. Saba*

University of California San Francisco Benioff Children’s Hospital Oakland, Children’s Hospital Oakland Research Institute, Oakland, USA

After undergoing positive and negative selection in the thymus, surviving mature T cells egress from the thymic parenchyma and enter the bloodstream to participate in adaptive immunity. Thymic egress requires signals mediated by sphingosine-1-phosphate (S1P), a bioactive lipid that serves as the ligand for a family of G protein-coupled receptors (S1P1-5) expressed on many cell types, including T cells. In the final stage of their development, T cells upregulate S1P1 expression on the cell surface, which enables them to recognize and respond to a chemotactic S1P gradient that lures them into the bloodstream. The gradient is generated by an S1P source close to the site of egress combined with an S1P sink generated by the actions of S1P catabolic enzymes including S1P lyase (SPL), the only enzyme that irreversibly degrades S1P. The requisite contribution of SPL to thymic egress is demonstrated by the profound lymphopenia observed in SPL knockout (KO) mice and wild type mice treated with SPL inhibitors. SPL is robustly expressed in thymic epithelial cells (TECs), which make up the stromal reticular network of the thymus. However, TEC SPL was recently found to be dispensable for thymic egress. In contrast, deletion of SPL in dendritic cells (DCs) — which represent only a small percent of thymic stroma — disrupts the S1P gradient and blocks thymic egress. These recent observations identify DCs as homeostatic regulators of thymic export through the actions of SPL, thereby adding one more piece to the complex puzzle of how S1P signaling contributes to the regulation of T cell trafficking.

DOI: 10.29245/2578-3009/2018/1.1103 View / Download Pdf

Quanquan Ding, Min Liu, Xiao-Lian Zhang*

State Key Laboratory of Virology and Medical Research Institute, Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology, Wuhan University College of Basic Medical Sciences, Wuhan 430071, P. R. China.

DOI: 10.29245/2578-3009/2018/1.1101 View / Download Pdf