A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism.
Foxp3(+) regulatory T (T reg) cells play a key role in controlling immune pathological re actions. Many develop their regulatory activity in the thymus, but there is also evidence for development of Foxp3(+) T reg cells from naive precursors in the periphery. Recent studies have shown that transforming growth factor (TGF)-beta can promote T reg cell development in culture, but little is known about the cellular and molecular mechanisms that mediate this pathway under more physiological conditions. Here, we show that after antigen activation in the intestine, naive T cells acquire expression of Foxp3. Moreover, we identify a population of CD103(+) mesenteric lymph node dendritic cells (DCs) that induce the development of Foxp3(+) T reg cells. Importantly, promotion of T reg cell responses by CD103(+) DCs is dependent on TGF-beta and the dietary metabolite, retinoic acid (RA). These results newly identify RA as a cofactor in T reg cell generation, providing a mechanism via which functionally specialized gut-associated lymphoid tissue DCs can extend the repertoire of T reg cells focused on the intestine.
Coombes
Janine L
JL
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
Siddiqui
Karima R R
KR
Arancibia-Cárcamo
Carolina V
CV
Hall
Jason
J
Sun
Cheng-Ming
CM
Belkaid
Yasmine
Y
Powrie
Fiona
F
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002469:Cell Separation; D003713:Dendritic Cells / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000502:physiology*; D039001:Integrin alpha Chains / Q000096:biosynthesis*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D008954:Models, Biological; D013601:T-Lymphocytes / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*
D015703:Antigens, CD; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D039001:Integrin alpha Chains; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; C091367:alpha E integrins; D014212:Tretinoin