Cellular immunity requires proper maintenance and differentiation of the precursors of haemocytes – blood cells – in the fly lymph gland, which contains an extensive network of extracellular matrix (ECM). The remodelling of this ECM controls blood progenitor behaviour, but how this is achieved remains unclear. Here, Kwang-Min Choe and colleagues study the role of Papilin, an abundant matrix glycoprotein, in haematopoiesis in fly lymph glands. The researchers observe that Papilin-knockdown larvae form melanotic masses and haemocyte differentiation is increased in lymph glands. Through tissue-specific knockdown experiments, they identify plasmatocytes as the main source of Papilin in lymph glands and fat bodies. The spatial arrangement of Papilin closely resembles that of ECM components collagen IV, laminin, nidogen and perlecan, and upon immune challenge Papilin structural organisation collapses, correlating with haemocyte differentiation. Knocking down Papilin leads to breakdown of the lymph gland ECM structure, but perlecan overexpression can partially rescue phenotypes caused by Papilin depletion. Finally, the researchers manipulate several signalling pathways known to affect lymph gland homeostasis and find that Papilin regulates prohaemocyte differentiation partly through the EGFR signalling pathway. Overall, the findings highlight how the ECM plays a role in maintaining the haematopoietic progenitor pool for appropriate immune response.
