The intestinal micro-environment imprints stromal cells to promote efficient Treg induction in gut-draining lymph nodes.
De novo induction of Foxp3⁺ regulatory T cells (Tregs) is particularly efficient in gut-draining mesenteric and celiac lymph nodes (mLN and celLN). Here we used LN transplantations to dissect the contribution of stromal cells and environmental factors to the high Treg-inducing capacity of these LN. After transplantation into the popliteal fossa, mLN and celLN retained their high Treg-inducing capacity, whereas transplantation of skin-draining LN into the gut mesenteries did not enable efficient Treg induction. However, de novo Treg induction was abolished in the absence of dendritic cells (DC), indicating that this process depends on synergistic contributions of stromal and DC. Stromal cells themselves were influenced by environmental signals as mLN grafts taken from germ-free donors and celLN grafts taken from vitamin A-deficient donors did not show any superior Treg-inducing capacity. Collectively, our observations reveal a hitherto unrecognized role of LN stromal cells for the de novo induction of Foxp3⁺ Tregs.
Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
S
S
Cording
Institute of Immunology, Hannover Medical School, Hannover, Germany.
B
B
Wahl
Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
D
D
Kulkarni
Institute of Immunology, Hannover Medical School, Hannover, Germany.
H
H
Chopra
Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
J
J
Pezoldt
Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
M
M
Buettner
Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
A
A
Dummer
Institute of Immunology, Hannover Medical School, Hannover, Germany.
U
U
Hadis
Institute of Microbiology and Hygiene, Charité University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
M
M
Heimesaat
Institute of Microbiology and Hygiene, Charité University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.
S
S
Bereswill
Transplantation Immunology, IFB-Tx, Hannover Medical School, Hannover, Germany.
C
C
Falk
1] Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany [2] Experimental Rheumatology, German Rheumatism Research Center Berlin and Charité University Medicine Berlin, Campus Mitte, Berlin, Germany.
U
U
Bode
Transplantation Immunology, IFB-Tx, Hannover Medical School, Hannover, Germany.
A
A
Hamann
Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
D
D
Fleissner
Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
J
J
Huehn
Institute of Immunology, Hannover Medical School, Hannover, Germany.
O
O
Pabst
D000818:Animals; D002450:Cell Communication; D060833:Cellular Microenvironment / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007108:Immune Tolerance; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D007422:Intestines / Q000166:cytology* / Q000276:immunology* / Q000382:microbiology; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015850:Interleukin-6; D014801:Vitamin A; D050697:Retinal Dehydrogenase