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Expansion of tolerogenic dendritic cells in neonatal lungs programs lymph node maturation, but impairs T cell proliferation

ABSTRACT: Multiple mechanisms restrain inflammation in neonates, most likely to prevent tissue damage caused by overly robust immune responses against newly encountered pathogens. Here, we identify a population of pulmonary dendritic cells (DCs) that express intermediate levels of CD103 (CD103int) and appear in the lungs and lung-draining lymph nodes of mice between birth and 2 weeks of age. CD103int DCs express XCR1 and CD205 and require expression of the transcription factor BATF3 for development, suggesting that they belong to the cDC1 lineage. In addition, CD103int DCs express CCR7 constitutively and spontaneously migrate to the lung-draining lymph node, where they promote stromal cell maturation and lymph node expansion. CD103int DCs mature independently of microbial exposure and TRIF- or MyD88-dependent signaling and are transcriptionally related to efferocytic and tolerogenic DCs as well as mature, regulatory DCs. Correlating with this, CD103int DCs show limited ability to stimulate proliferation and IFN-γ production by CD8+ T cells. Moreover, CD103int DCs acquire apoptotic cells efficiently, in a process that is dependent on the expression of the TAM receptor, Mertk, which drives their homeostatic maturation. The appearance of CD103int DCs coincides with a temporal wave of apoptosis in developing lungs and explains, in part, dampened pulmonary immunity in neonatal mice. Together, these data suggest a mechanism by which DCs sense apoptotic cells at sites of noninflammatory tissue remodeling, such as tumors or the developing lungs, and limit local T cell responses.

ORGANISM(S): Mus musculus

PROVIDER: GSE112270 | GEO | 2023/03/24

REPOSITORIES: GEO

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Gene expression profile at single cell level of dendritic cells (DC) from the lung of neonatal (NEO) or adult (AD) mice

Project description:Multiple mechanisms restrain inflammation in neonates. Here we identify a population of pulmonary dendritic cells (DCs) that appear in the lungs and lung−draining lymph nodes between birth and two weeks of age and express intermediate levels of CD103 (CD103int). CD103int DCs express XCR1, CD205, and require the transcription factor, Batf3, suggesting that they belong to the cDC1 lineage. They also constitutively express CCR7 and spontaneously migrate to the lung−draining lymph node, where they promote stromal cell maturation and lymph node expansion, independently of microbial exposure and Trif− or MyD88−dependent signaling. CD103int DCs are transcriptionally related to efferocytic and tolerogenic DCs as well as mature, regulatory DCs. CD103int DCs efficiently acquire apoptotic cells and become activated through Mertk signaling, which also impairs CD8+ T cell activation. The appearance of CD103int DCs coincides with a temporal wave of apoptosis in developing lungs and explains, in part, impaired pulmonary immunity in neonatal mice.

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