Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/652032

Fate mapping via Ms4a3 expression history traces monocyte-derived cells

Liu, Z.·Gu, Y.·Chakarov, S.·Bleriot, C.·Chen, X.·Shin, A.·Huang, W.·Dress, R. J.·Dutertre, C. A.·Schlitzer, A.·Chen, J.·Wang, H.·Su, B.·Ginhoux, F.
View original source ↗Export metadata ↓

Abstract

Most tissue-resident macrophage (RTM) populations are seeded by waves of embryonic hematopoiesis and are self-maintained independently of a bone-marrow contribution during adulthood. A proportion of RTMs, however, is constantly replaced by blood monocytes and their functions compared to embryonic RTM remains unclear. The kinetics and extent of the contribution of circulating monocytes to RTM replacement during homeostasis, inflammation and disease is highly debated. Here, we identified Ms4a3 as a specific marker expressed by granulocyte-monocyte progenitors (GMPs) and subsequently generated Ms4a3TdT reporter and Ms4a3Cre-RosaTdT fate mapper models to follow monocytes and their progenies. Our Ms4a3Cre-RosaTdT model traced efficiently blood monocytes (97%) and granulocytes (100%), but no lymphocytes or tissue dendritic cells. Using this model, we precisely quantified the contribution of monocytes to the RTM pool during homeostasis and inflammation. The unambiguous identification of monocyte-derived cells will permit future studies of their function under any condition.

Source connections

Explore related subjects

immunologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Liu, Z., Gu, Y., Chakarov, S., Bleriot, C., Chen, X., Shin, A., Huang, W., Dress, R. J., Dutertre, C. A., Schlitzer, A., Chen, J., Wang, H., Su, B., Ginhoux, F.. 2019-05-27. Fate mapping via Ms4a3 expression history traces monocyte-derived cells. https://doi.org/10.1101/652032

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Clonally Convergent Tph/Tfh-like CD4+ T Cells are Shared Across Recovery and Recurrence in Experimental Periodontitis

Periodontitis is a chronic inflammatory disease of the tooth-supporting structures (periodontium) that requires life-long maintenance to prevent progression. Using a sensitized model of recurrent periodontitis in mice (SeRPD), in which regulatory breakdown was induced by temporary Treg depletion concurrent with disease, we mapped the gingival T cell imprint across each disease phase. Transient regulatory breakdown left a durable mucosal imprint after clinical recovery, characterized by enrichment of local and regional CD4 T cells. Paired single-cell RNA and TCR sequencing of gingival immune cells identified a convergent clonotype expanded from recovery into recurrence that carried a Tfh/Tph-like transcriptional identity. An analogous CD4 T cell population was detected in human periodontitis lesions by single-cell transcriptomics. Together, these findings support a paradigm in which clinical recovery does not ensure a local T cell repertoire reset; instead, a reservoir of antigen-experienced, tissue-adapted CD4 T cells persist in the mucosa and participate in recurrence.

immunology↗
bioRxiv2026

Robust T and B cell activation is associated with rapid clearance of infectious SARS-CoV-2

The immunologic correlates of rapid clearance of SARS-CoV-2 shedding are not well understood, partly due to challenges of collecting samples early after infection and the fact that most studies do not measure infectious virus. Here, we performed mass cytometry profiling of peripheral blood cells collected from people 4-6 days after onset of symptoms from acute SARS-CoV-2 infection who underwent daily nasopharyngeal testing for SARS-CoV-2 culture positivity. We identified broad and coordinated activation of innate and adaptive immune cells in unvaccinated individuals with primary infection. Faster clearance of infectious virus shedding was associated with robust adaptive immune cell activation and proliferation, namely among cytotoxic CD8+, CD4+, and {gamma}{delta} T cells and plasmablasts. In contrast, vaccinated individuals who rapidly cleared breakthrough infection showed minimal cellular immune activation. Our findings identify early immune correlates of rapid clearance of infectious SARS-CoV-2 shedding that may inform future prevention and therapeutic approaches to reduce disease burden and transmission.

immunology↗
bioRxiv2026

Live attenuated YFV-17D vaccine induces robust B and T cell immunity in vaccine-draining lymph nodes

The yellow fever virus-17D (YFV-17D) vaccine is widely regarded as one of the most effective vaccines in existence, with protection linked to robust elicitation of neutralising antibodies1. The features of the germinal centre (GC) reaction driving this durable and potent antibody responses remain unclear. Here we examined immune dynamics in blood and lymph nodes (LNs) after primary YFV-17D immunisation in humans. Using fine needle biopsy (FNB), we identified robust T and B lymphocyte responses within draining LNs, underpinning maturation of antibodies targeting the viral envelope (E). Early antibody responses were largely IgM, with gradual accumulation of E-specific memory B cells and anti-viral IgG in the subsequent months. Monoclonal antibodies derived from GC B cells had specificity for E, with diversification in the LN capable of driving increases in binding and neutralising potency. While circulating vaccine-specific CD4+ T cells peaked two weeks post-vaccination, clonally related GC and IL-10+ T follicular helper populations progressively accumulated in the LN. Comparison of FNB transcriptional datasets following YFV-17D, SARS-CoV-2 mRNA/LNP, and seasonal influenza vaccination identified a conserved GC program involving similar B and T lymphocyte subpopulations. Collectively, we find that while YFV-17D induces robust GC activity, this trait is shared with other vaccine platforms and the notably durable protection against infection may reflect an incapacity of the virus to escape host immunity.

immunology↗