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Biology subjects

Weier, A.-K.

Publications and source records attributed to Weier, A.-K..

2 recordsLinked to original sources

Multiple clustered centrosomes in antigen-presenting cells foster T cell activation without MTOC polarization

Cellular polarization plays a pivotal role in regulating immunological processes and is often associated with centrosome reorientation. During immune synapse (IS) formation centrosome repositioning in lymphocytes assists in T cell activation. While a single centrosome, consisting of two centrioles, is present in T cells, antigen-presenting cells (APCs) such as dendritic cells (DCs) amplify centrioles during maturation leading to increased centrosome numbers upon immune activation. How centrosome amplification in DCs affects IS formation and T cell activation is unclear. In this study, we combine experimental data with mathematical and computational modelling to provide evidence that centrosome amplification in DCs enhances antigen-specific T cell activation. Extra centrioles in DCs form active centrosomes, which cluster during DC-T cell interactions and unlike in T cells, localize close to the cell center. Perturbing either centriole numbers or centrosome configuration in DCs results in impaired T cell activation. Collectively, our results highlight a crucial role for centrosome amplification and optimal centrosome positioning in APCs for controlling T cell responses.

cell biology↗

GPR183 targets lung-resident CD301b+ conventional dendritic cells type 2 to a subtissular TSLP-TSLP receptor-mediated survival niche within the adventitial cuff

Conventional dendritic cells (cDCs) are strategically localized throughout non-lymphoid tissues. How such spatially regulated subtissular placement is achieved remains largely elusive. Here, we reveal that GPR183 targets CD301b+ cDC2 to a TSLP-dependent survival niche within the adventital cuff. We identified a close association of CD301b+ cDC2 with PDGFR+ fibroblasts within the adventitial region of the lung. Genetic ablation of GPR183 within the cDC lineage leads to a selective loss of CD301b+ cDC2 in conjunction with the loss of CD301b+ cDC2 : fibroblast colocalization. Next bone marrow chimeric experiments and expression studies suggested adventitial fibroblasts as the main source of 7,25 hydroxycholesterol, the natural ligand of GPR183. Single cell transcriptomic receptor ligand inference and subsequent genetic validation revealed TSLP receptor signalling as a crucial fibroblast derived CD301b+ cDC2 survival factor. These data expose a subtissular localization mechanism for tissue-specific functionalization of CD301b+ cDC2.

immunology↗