The Spleen Is Indispensable For The Immunosuppressive Activity Of Mesenchymal Stromal Cells In Ova Allergic Asthma
In the past decade, mesenchymal stromal cells (MSCs) have developed a substantial portfolio in clinical trials, becoming the focus of many regenerative immunotherapies. Besides being multipotent and having self-renewal capacity, MSCs possess anti-inflammatory properties. However, the mechanisms underlying their immunosuppressive effects remain poorly understood. We showed that upon intravenous (i.v.) administration, MSCs localise to the lungs and undergo caspase 3-dependent apoptosis within 1 hour. Furthermore, efferocytosis of apoptotic MSCs modulated the effector functions of lung phagocytes, especially alveolar macrophages. Secondary lymphoid organs, such as the spleen, are responsible for trapping foreign antigens entering via bloodstream. Therefore, we expected to see the spleen as central to the establishment of anti-inflammatory effects seen in MSC therapy. In an OVA-induced allergic asthma model, the immunosuppressive effects of MSC administration were abrogated in splenectomised mice. MSCs failed to inhibit lung eosinophilia and OVA-specific T cell restimulation responsiveness, including IL-5 and IL-13 production, in splenectomised mice. Splenectomised mice treated with MSCs had comparable levels of mucous production to their untreated counterparts, evident through lung histology. Overall, the spleen is indispensable for the immunosuppressive effects of i.v.-injected MSCs in OVA allergic asthma.