Intestinal CD103+, but not CX3CR1+, antigen sampling cells migrate in lymph and serve classical dendritic cell functions

By O. Schulz, E. Jaensson, E. Persson, Xiaosun Liu, T. Worbs, W. Agace, O. Pabst. Journal of Experimental Medicine, 2009

715 citations recorded by the source corpus.

Chemokine receptor CX3CR1+ dendritic cells (DCs) have been suggested to sample intestinal antigens by extending transepithelial dendrites into the gut lumen. Other studies identified CD103+ DCs in the mucosa, which, through their ability to synthesize retinoic acid (RA), appear to be capable of generating typical signatures of intestinal adaptive immune responses. We report that CD103 and CX3CR1 phenotypically and functionally characterize distinct subsets of lamina propria cells. In contrast to CD103+ DC, CX3CR1+ cells represent a nonmigratory gut-resident population with slow turnover rates and poor responses to FLT-3L and granulocyte/macrophage colony-stimulating factor. Direct visualization of cells in lymph vessels and flow cytometry of mouse intestinal lymph revealed that CD103+ DCs, but not CX3CR1-expressing cells, migrate into the gut draining mesenteric lymph nodes (LNs) under steady-state and inflammatory conditions. Moreover, CX3CR1+ cells displayed poor T cell stimulatory capacity in vitro and in vivo after direct injection of cells into intestinal lymphatics and appeared to be less efficient at generating RA compared with CD103+ DC. These findings indicate that selectively CD103+ DCs serve classical DC functions and initiate adaptive immune responses in local LNs, whereas CX3CR1+ populations might modulate immune responses directly in the mucosa and serve as first line barrier against invading enteropathogens.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/4d54aac721fd3c6c7d90df486efa2e6ae2d17340

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In Immunology

1. Florent Ginhoux
2. Steffen Jung
3. C. Varol
4. Miriam Merad
5. Eric G. Pamer
6. C. Shi
7. M. Mack
8. Werner Müller

Citations in the corpus

• The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. (2013, background): “For instance, in the muscle, expression of FcγRI helps distinguish between these two subpopulations (40), whereas expression of CD103 helps distinguish between the two CD11b+ cDC subsets in the lamina propria (31, 41).”
• International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors (2014, neutral): “Human DCs are subdivided into CD104+ plasmacytoid DCs and conventional (or myeloid) CD11c+ DCs, the latter consisting of a CD16+ subset (;70%), a CD1c+ (also called BDCA-1 from blood dendritic cell antigen-1) subset (;30%), and a CD141+ (thrombomodulin, also called BDCA-3) subset (,5”
• Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. (2012, methodology): “Interestingly, microarray analysis revealed that Ly6C cells also prominently express CD135, the receptor for the cytokine Fms-related tyrosine kinase 3 ligand (Flt3L), known to be critical for cDC development and homeostasis (Bogunovic et al., 2009; Saunders et al., 1996; Schulz et al., 2009).”
• Monocyte recruitment during infection and inflammation (2011, background): “Instead, CD103 + DCs, which express high levels of CCR7, carry antigen into draining mesenteric lymph nodes, where they prime T cell”
• IRF4 Transcription Factor-Dependent CD11b+ Dendritic Cells in Human and Mouse Control Mucosal IL-17 Cytokine Responses (2013, result): “Similar to LLN, the CD11b+ fraction of migratory DCs (CD11cloMHCIIhi) in the mesenteric lymphnodes (MLN) expressed CD24 and not CD64, suggesting that only the CD11b+CD24+CD64 fraction migrates toMLN (Figure 4B), as previously reported (Bogunovic et al., 2009; Schulz et al., 2009).”
• Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria. (2011, background): “CD11c+MHCII+CD103+ DCs and F4/80+CD11b+ macrophages were present at similar numbers in CX3CR1-deficient and wild-type mice when analyzed by flow cytometry and immunofluorescence microscopy (Figure 5A and data not shown) and expressed similar levels of costimulatory molecules CD40, CD80, and CD86 as ”