Mouse mesenchymal stem cells inhibit high endothelial cell activation and lymphocyte homing to lymph nodes by releasing TIMP-1.

Mesenchymal stem cells (MSC) represent a promising therapeutic approach in many diseases in view of their potent immunomodulatory properties, which are only partially understood. Here, we show that the endothelium is a specific and key target of MSC during immunity and inflammation. In mice, MSC inhibit activation and proliferation of endothelial cells in remote inflamed lymph nodes (LNs), affect elongation and arborization of high endothelial venules (HEVs) and inhibit T-cell homing. The proteomic analysis of the MSC secretome identified the tissue inhibitor of metalloproteinase-1 (TIMP-1) as a potential effector molecule responsible for the anti-angiogenic properties of MSC. Both in vitro and in vivo, TIMP-1 activity is responsible for the anti-angiogenic effects of MSC, and increasing TIMP-1 concentrations delivered by an Adeno Associated Virus (AAV) vector recapitulates the effects of MSC transplantation on draining LNs. Thus, this study discovers a new and highly efficient general mechanism through which MSC tune down immunity and inflammation, identifies TIMP-1 as a novel biomarker of MSC-based therapy and opens the gate to new therapeutic approaches of inflammatory diseases

Whoonga: Potential Recreational Use of HIV Antiretroviral Medication in South Africa

Whoonga is a drug cocktail in South Africa rumored to contain illicit drugs and HIV antiretroviral (ARV) medication. Although its use may adversely impact adherence to HIV treatment and may have the potential to generate ARV resistance, there is a paucity of research characterizing whoonga. We learned of whoonga during semi-structured interviews about substance abuse and HIV risk at “club-events” known as inkwaris in an urban township of Durban, South Africa. Whoonga was an emerging theme spontaneously identified as a problem for the community by 17 out of 22 informants. Perceptions of whoonga suggest that it is highly addictive, contains ARVs (notably efavirenz), is used by individuals as young as 14, and poses a threat to the health and safety of those who use it, including increasing the risk of HIV infection. Our informants provide preliminary evidence of the dangers of whoonga and reinforce the need for further study

Chemokines and integrins independently tune actin flow and substrate friction during intranodal migration of T cells.

Although much is known about the physiological framework of T cell motility, and numerous rate-limiting molecules have been identified through loss-of-function approaches, an integrated functional concept of T cell motility is lacking. Here, we used in vivo precision morphometry together with analysis of cytoskeletal dynamics in vitro to deconstruct the basic mechanisms of T cell migration within lymphatic organs. We show that the contributions of the integrin LFA-1 and the chemokine receptor CCR7 are complementary rather than positioned in a linear pathway, as they are during leukocyte extravasation from the blood vasculature. Our data demonstrate that CCR7 controls cortical actin flows, whereas integrins mediate substrate friction that is sufficient to drive locomotion in the absence of considerable surface adhesions and plasma membrane flux