Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid.
To maintain immune homeostasis, the intestinal immune system has evolved redundant regulatory strategies. In this regard, the gut is home to a large number of regulatory T (T reg) cells, including the Foxp3(+) T reg cell. Therefore, we hypothesized that the gut environment preferentially supports extrathymic T reg cell development. We show that peripheral conversion of CD4(+) T cells to T reg cells occurs primarily in gut-associated lymphoid tissue (GALT) after oral exposure to antigen and in a lymphopenic environment. Dendritic cells (DCs) purified from the lamina propria (Lp; LpDCs) of the small intestine were found to promote a high level of T reg cell conversion relative to lymphoid organ-derived DCs. This enhanced conversion by LpDCs was dependent on TGF-beta and retinoic acid (RA), which is a vitamin A metabolite highly expressed in GALT. Together, these data demonstrate that the intestinal immune system has evolved a self-contained strategy to promote T reg cell neoconversion.
Sun
Cheng-Ming
CM
Mucosal Immunology Unit, Laboratory of Parasitic Diseases, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Hall
Jason A
JA
Blank
Rebecca B
RB
Bouladoux
Nicolas
N
Oukka
Mohamed
M
Mora
J Rodrigo
JR
Belkaid
Yasmine
Y
D000284:Administration, Oral; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology; D051858:Forkhead Transcription Factors / Q000378:metabolism* / Q000502:physiology*; D007107:Immune System; D007421:Intestine, Small / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D014212:Tretinoin