Biology subjects

Tatsumi, N.

Publications and source records attributed to Tatsumi, N..

3 recordsLinked to original sources

bioRxiv2023

Rapid activation of IL-2 receptor signaling by CD301b+DC-derived IL-2 dictates the outcome of helper T cell differentiation

Effector T helper (Th) cell differentiation is fundamental to functional adaptive immunity. Different subsets of dendritic cells (DCs) preferentially induce different types of Th cells, but the fate instruction mechanism for Th type 2 (Th2) differentiation remains enigmatic, as the critical DC-derived cue has not been clearly identified. Here, we show that CD301b+ DCs, a major Th2-inducing DC subset, drive Th2 differentiation through cognate interaction by kick-starting IL-2 receptor signaling in CD4T cells. Mechanistically, CD40 engagement induces IL-2 production selectively from CD301b+ DCs to maximize CD25 expression in CD4 T cells, which is required specifically for the Th2 fate decision. On the other hand, CD25 in CD301b+ DCs facilitates directed action of IL-2 toward cognate CD4T cells. Furthermore, CD301b+ DC-derived IL-2 skews CD4T cells away from the T follicular helper fate. These results highlight the critical role of DC-intrinsic CD40-IL-2 axis in bifurcation of Th cell fate.

immunology↗

bioRxiv2022

Lung evolution in vertebrates and the water-to-land transition

A crucial evolutionary change in vertebrate history was the Palaeozoic (Devonian ~400 million years ago) water-to-land transition, allowed by key morphological and physiological modifications including the acquisition of lungs. Nonetheless, the origin and early evolution of vertebrate lungs remain highly controversial, particularly whether the ancestral state was paired or unpaired. Due to the rarity of fossil soft tissue preservation, lung evolution can only be traced based on the extant phylogenetic bracket. Here we investigate, for the first time, lung morphology in extensive developmental series of key living lunged osteichthyans using synchrotron X-ray microtomography and histology. Our results shed light on the primitive state of vertebrate lungs as unpaired, evolving to be truly paired in the lineage towards the tetrapods. The water-to-land transition confronted profound physiological challenges and paired lungs were decisive for increasing the surface area and the pulmonary compliance and volume, especially during the air-breathing on land.

evolutionary biology↗

bioRxiv2020

Optimal CD4T Cell Priming in Lymph Nodes Requires Repertoire Scanning by CD301b+ Migratory cDC2 Cells

Activation of CD4T cells by conventional dendritic cells (cDC) is pivotal in adaptive immunity. However, while the activation mechanism of antigen-specific CD4T cells has been extensively studied, the cellular mechanism that leads to the selection of cognate CD4T cell clones out of the polyclonal pool is incompletely understood. Here, we show that, in the reactive lymph nodes, newly homed naive polyclonal CD4T cells are temporarily retained before leaving the lymph node. This stop-and-go traffic of CD4T cells provides an adequate time window for efficient scanning and timely priming of antigen-specific clones. Mechanistically, upon immunization, CD301b+ DCs, a major subset of migratory cDC2 cells, quickly migrate to the draining lymph node and settle in the areas near the high endothelial venules, where they retain incoming polyclonal CD4T cells through MHCII-dependent but antigen-independent mechanisms while concurrently providing cognate stimuli to prime antigen-specific CD4T cells. These results indicate that CD301b+ DCs function as an immunological "display window" for CD4T cells to efficiently scan their antigen specificity. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/276410v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@118d9b7org.highwire.dtl.DTLVardef@7daf2eorg.highwire.dtl.DTLVardef@17808c0org.highwire.dtl.DTLVardef@186780e_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LINewly homed polyclonal CD4T cells are temporarily retained in the reactive lymph nodes. C_LIO_LIDepletion of CD301b+ DCs results in shorter dwell time of CD4T cells in the draining lymph node and delayed priming of antigen-specific clones. C_LIO_LIThe transient retention of polyclonal CD4T cells in the draining lymph node requires MHCII expression on CD301b+ DCs but not cognate antigen. C_LIO_LICD301b+ DCs are required for robust expansion of rare antigen-specific CD4T cell clones and their skewing toward Th2 cells. C_LI

immunology↗