TY - JOUR TI - Platelets orchestrate the resolution of pulmonary inflammation in mice by T reg cell repositioning and macrophage education AU - Rossaint, Jan AU - Thomas, Katharina AU - Mersmann, Sina AU - Skupski, Jennifer AU - Margraf, Andreas AU - Tekath, Tobias AU - Jouvene, Charlotte C. AU - Dalli, Jesmond AU - Hidalgo, Andres AU - Meuth, Sven G. AU - Soehnlein, Oliver AU - Zarbock, Alexander T2 - Journal of Experimental Medicine AB - Beyond hemostasis, platelets actively participate in immune cell recruitment and host defense, yet their potential in the resolution of inflammatory processes remains unknown. Here, we demonstrate that platelets are recruited into the lung together with neutrophils during the onset of inflammation and alongside regulatory T (T reg) cells during the resolution phase. This partnering dichotomy is regulated by differential adhesion molecule expression during resolution. Mechanistically, intravascular platelets form aggregates with T reg cells, a prerequisite for their recruitment into the lung. This interaction relies on platelet activation by sCD40L and platelet P-selectin binding to PSGL-1 on T reg cells. Physical platelet–T reg cell interactions are necessary to modulate the transcriptome and instruct T reg cells to release the anti-inflammatory mediators IL-10 and TGFβ. Notably, the presence of platelet–T reg cell aggregates in the lung was also required for macrophage transcriptional reprogramming, polarization toward an anti-inflammatory phenotype, and effective resolution of pulmonary inflammation. Thus, platelets partner with successive immune cell subsets to orchestrate both the initiation and resolution of inflammation. DA - 2021/05/20/ PY - 2021 DO - 10.1084/jem.20201353 DP - Silverchair VL - 218 IS - e20201353 J2 - Journal of Experimental Medicine SN - 0022-1007 UR - https://doi.org/10.1084/jem.20201353 Y2 - 2021/05/21/16:59:31 ER -