Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans.
A functionally distinct subset of CD103(+) dendritic cells (DCs) has recently been identified in murine mesenteric lymph nodes (MLN) that induces enhanced FoxP3(+) T cell differentiation, retinoic acid receptor signaling, and gut-homing receptor (CCR9 and alpha4beta7) expression in responding T cells. We show that this function is specific to small intestinal lamina propria (SI-LP) and MLN CD103(+) DCs. CD103(+) SI-LP DCs appeared to derive from circulating DC precursors that continually seed the SI-LP. BrdU pulse-chase experiments suggested that most CD103(+) DCs do not derive from a CD103(-) SI-LP DC intermediate. The majority of CD103(+) MLN DCs appear to represent a tissue-derived migratory population that plays a central role in presenting orally derived soluble antigen to CD8(+) and CD4(+) T cells. In contrast, most CD103(-) MLN DCs appear to derive from blood precursors, and these cells could proliferate within the MLN and present systemic soluble antigen. Critically, CD103(+) DCs with similar phenotype and functional properties were present in human MLN, and their selective ability to induce CCR9 was maintained by CD103(+) MLN DCs isolated from SB Crohn's patients. Thus, small intestinal CD103(+) DCs represent a potential novel target for regulating human intestinal inflammatory responses.
Jaensson
Elin
E
Immunology Section, BMC D14, 221 84 Lund University, Lund, Sweden.
Uronen-Hansson
Heli
H
Pabst
Oliver
O
Eksteen
Bertus
B
Tian
Jiong
J
Coombes
Janine L
JL
Berg
Pia-Lena
PL
Davidsson
Thomas
T
Powrie
Fiona
F
Johansson-Lindbom
Bengt
B
Agace
William W
WW
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D002478:Cells, Cultured; D017124:Conserved Sequence; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D039001:Integrin alpha Chains / Q000096:biosynthesis*; D016023:Integrins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D054388:Receptors, CCR / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
D015703:Antigens, CD; C119309:CC chemokine receptor 9; D039001:Integrin alpha Chains; D016023:Integrins; D054388:Receptors, CCR; C091367:alpha E integrins; C071777:integrin alpha4beta7