Epithelial colonization by gut dendritic cells promotes their functional diversification

Rivera, Claudia A; Randrian, Violaine; Richer, Wilfrid; Gerber-Ferder, Yohan; Delgado, Maria–Graciela; Chikina, Aleksandra; Frede, Annika; Sorini, Chiara; Maurin, Mathieu; Kammoun-Chaari, Hana; Parigi, Sara Martina; Goudot, Christel; Cabeza-Cabrerizo, Mar; Baulande, Sylvain; Lameiras, Sonia; Guermonprez, Pierre; Sousa, Caetano Reis e; Lecuit, Marc; Moreau, Hélène D.; Helft, Julie; Vignjević, Danijela; Villablanca, Eduardo J.; Lennon-Duménil, Ana-María

doi:10.1016/j.immuni.2021.11.008

Cited by 38 publications

(26 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These neonatal cDC2 interacted with the epithelium and exhibited membrane extensions towards the FAE surface suggesting an active role in antigen uptake. Similar to what has recently been described in the adult intestinal mucosa, these epithelium-associated cDC2 might be less mature and promote T cell hypo-responsiveness contributing to delayed immune maturation (Rivera et al, 2021).…”

Section: Discussionsupporting

confidence: 58%

Neonatal Peyer’s patch cDC activation as a pacemaker of postnatal immune maturation

Torow

Hitch

et al. 2022

Preprint

View full text Add to dashboard Cite

Marked differences exist between the mucosal immune system of the neonate and adult host. The pronounced influence of the enteric microbiota in adults suggests a causal relationship between postnatal colonization and immune maturation. However, using metagenomic, metaproteomic, and functional immunological analyses we demonstrate an early presence of bacteria and immunogenic microbial antigens preceding immune maturation in the small intestine, the primary inductive site of intestinal immunity. Instead, transcriptomic, flow cytometric and histological analysis indicated neonatal Peyer’s patch (PP) mononuclear phagocytes (MNP) as rate limiting factor of postnatal immune maturation. Despite the early presence of MNPs, conventional dendritic cells (cDC) of type 1, 2a and 2b exhibited significant age-dependent differences in tissue distribution and cellular composition. Single cell transcriptional profiling and functional assays revealed decreased antimicrobial and antigen processing/presentation capacity, an overall retarded cell maturation and reduced antigen uptake. In cDC2a this resulted in a reduced proportion of CCR7+ migratory cells and a consequent defect in CD4 T cell priming. Interestingly, transcriptional profiling of neonatal DC subsets identified reduced expression of type I interferon (IFN)-stimulated genes (ISG). Type I IFN induction by oral administration of the TLR7 agonist R848 accelerated MNP maturation and enhanced cognate antigen CD4 T cell priming. However, humoral responses to oral vaccination in the presence of R848 were significantly reduced. Together, our results identify PP MNP maturation as pacemaker of postnatal mucosal immune priming, indicate the biological role of delayed maturation and demonstrate that targeted interventional strategies allow manipulation of mucosal responses in early life.

show abstract

Section: Discussionsupporting

confidence: 58%

Neonatal Peyer’s patch cDC activation as a pacemaker of postnatal immune maturation

Torow

Hitch

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…In the spleen and the intestine Notch2 and Ltβr have been reported to be important for cDC2 maintenance, its source being likely of non-hematopoietic origin (Lewis et al ., 2011; Satpathy et al ., 2013). More recently retinoic acid and the transition from a mucosal to a epithelial location within the colon was linked to the maturation status of cDC2 (Rivera et al, 2021). Furthermore, in the lung granulocyte macrophage colony stimulating factor (GMCSF) has been associated to the loss of cDC1s and to a lesser extend to that of cDC2 during homeostasis (Greter et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

GPR183 targets lung-resident CD301b⁺ conventional dendritic cells type 2 to a subtissular TSLP – TSLP receptor mediated survival niche within the adventital cuff

Zhang

Spath

et al. 2022

Preprint

View full text Add to dashboard Cite

Conventional dendritic cells (cDCs) are strategically localized throughout non-lymphoid tissues. How such spatially regulated subtissular placement is achieved remains largely elusive. Here, we reveal that GPR183 targets CD301b+ cDC2 to a TSLP-dependent survival niche within the adventitial cuff. We identified a close association of CD301b+ cDC2 with PDGFRα+ fibroblasts within the adventitial region of the lung. Genetic ablation of GPR183 within the cDC lineage leads to a selective loss of CD301b+ cDC2 in conjunction with the loss of CD301b+ cDC2 : fibroblast colocalization. Next bone marrow chimeric experiments and expression studies suggested adventitial fibroblasts as the main source of 7α,25 hydroxycholesterols, the natural ligand of GPR183. Single-cell transcriptomic receptor ligand inference and subsequent genetic validation revealed TSLP receptor signaling as a crucial fibroblast-derived CD301b+ cDC2 survival factor. These data expose a subtissular localization mechanism for tissue-specific functionalization of CD301b+ cDC2.

show abstract

“…Deletion of TGFβR1 in DCs resulted in a strong reduction of the intestinal CD103 + CD11b + population with a corresponding increase in CD103 – CD11b + migDC2s, together with decreased frequencies of Treg populations that promote tolerance to food antigens, and reduced frequencies of lamina propria Th17 cells [31]. Within the CD103 + CD11b + migDC2 subset, further diversification is associated with the precise location within the intestinal mucosa, with intra‐epithelial migDC2s expressing an immature phenotype due to local high ATRA concentrations, while lamina propria migDC2s express a mature, pro‐inflammatory phenotype [32].…”

Section: Specialization In Nonlymphoid Tissuementioning

confidence: 99%

IL‐13 in dermal type‐2 dendritic cell specialization: From function to therapeutic targeting

2022

View full text Add to dashboard Cite

Skin functions as a barrier protecting the host against physical, thermal, chemical changes as well as microbial insults. The skin is populated by several immune cell types that are crucial to host defense and to maintain self-tolerance as well as equilibrium with beneficial microbiota. Conventional dendritic cells (cDCs) are antigen-presenting cells that patrol the skin and all other nonlymphoid tissues for self or foreign antigens, and then migrate to draining lymph nodes to initiate T-cell responses. This review article describes recent developments on skin cDC specialization, focusing on the role of IL-13, a cytokine essential to allergic immune responses that is also secreted at steady state by type-2 innate lymphoid cells in healthy skin, and is required for dermal cDC differentiation. Furthermore, we contextualize how different therapeutics that block IL-13 signaling and were recently approved for the treatment of atopic dermatitis might affect cDCs in human skin.

show abstract

Epithelial colonization by gut dendritic cells promotes their functional diversification

Cited by 38 publications

References 57 publications

Neonatal Peyer’s patch cDC activation as a pacemaker of postnatal immune maturation

Neonatal Peyer’s patch cDC activation as a pacemaker of postnatal immune maturation

GPR183 targets lung-resident CD301b⁺ conventional dendritic cells type 2 to a subtissular TSLP – TSLP receptor mediated survival niche within the adventital cuff

IL‐13 in dermal type‐2 dendritic cell specialization: From function to therapeutic targeting

Contact Info

Product

Resources

About

Epithelial colonization by gut dendritic cells promotes their functional diversification

Cited by 38 publications

References 57 publications

Neonatal Peyer’s patch cDC activation as a pacemaker of postnatal immune maturation

Neonatal Peyer’s patch cDC activation as a pacemaker of postnatal immune maturation

GPR183 targets lung-resident CD301b+ conventional dendritic cells type 2 to a subtissular TSLP – TSLP receptor mediated survival niche within the adventital cuff

IL‐13 in dermal type‐2 dendritic cell specialization: From function to therapeutic targeting

Contact Info

Product

Resources

About

GPR183 targets lung-resident CD301b⁺ conventional dendritic cells type 2 to a subtissular TSLP – TSLP receptor mediated survival niche within the adventital cuff