De Leval, L. | bioRxiv Science

bioRxiv2024

Follicular Bcl6 reactivity is associated with a unique immune landscape and spatial transcriptome in COVID-19

The regulation of follicular (F) and germinal center (GC) immune reactivity in human lymph nodes (LNs), particularly during the early stages of viral infections, remains poorly understood. We have analyzed lung-draining lymph nodes (LD-LNs) from COVID-19 autopsies using multiplex imaging and spatial transcriptomics to examine the immune landscape and with respect to the aging. We identified three subgroups of Reactive Follicles (RFs) based on Bcl6 prevalence, RF-Bcl6no/low, RF-Bcl6int and RF-Bcl6high. RF-Bcl6high tissues express a distinct B/TFH immune landscape associated with increased prevalence of proliferating B- and TFH-cell subsets. Comparison between LD-LNs and matched subdiaphragmatic LNs revealed a disconnected Bcl6 reactivity between the two anatomical sites. LD-LNs Bcl6 reactivity was associated with a distinct spatial transcriptomic profile. TH1-associated genes/pathways (e.g. CXCR3, STAT5, TNF signaling) were significantly upregulated in RF-Bcl6no/low tissues while the RF-Bcl6high tissues exhibited significant upregulation of GC-promoting genes/pathways (e.g. CXCL13, B cell receptor signaling). Despite the similar prevalence, the in-situ transcriptome profiling indicates a higher monocyte/macrophage functionality in "Aged" compared to "Young" follicles from donors with comparable Bcl6 reactivity. Our findings reveal a heterogeneous F/GC landscape in COVID-19 LD-LNs and highlight specific molecular targets and pathways that could regulate human F/GC immune dynamics during early viral infections.

immunology↗

bioRxiv2023

Adrenal extramedullary hematopoiesis as an inducible model of the adult hematopoietic niche

Hematopoietic Stem and Progenitor Cells (HSPCs) reside in the hematopoietic niche, a structure that regulates the balance of cellular quiescence, self-renewal and commitment in a demand-adapted manner. The bone marrow (BM) hematopoietic niche is formed by several cellular players, mainly endothelial cells, osteoblasts, adipocytes, and stromal cells. While the BM niche forms a complex structure, evidence exists for simpler, albeit functional, extramedullary hematopoietic niches. However, the composition of what constitutes the simplest unit of an HSPC supportive microenvironment remains largely unknown. Here, we show that the adult adrenal gland can be transformed into a hematopoietic supportive environment. Upon splenectomy and hormonal stimulation, the adult adrenal gland can be induced to recruit and host HSPC function, including serial transplantation. Furthermore, the adrenal stroma contains a CXCL12+ population, reminiscent of BM CXCL12-Abundant Reticular (CAR) cells. Mirroring this, we found CXCL12+ cells in patient samples obtained from a local cohort of myelolipoma, a benign adrenal tumor composed of adipose and hematopoietic tissue that constitutes the most common site of extramedullary hematopoiesis specific to the adult. We present our model as a novel tool to increase our understanding of the physiology of hematopoietic support and to facilitate the development of a boneless niche model.

cell biology↗