IL-23 receptor regulates unconventional IL-17-producing T cells that control bacterial infections.
IL-23 plays an important role in autoimmune tissue inflammation and induces the generation of not fully characterized effector cells that mediate protection against pathogens. In this paper, we established the essential role of IL-23R in the host response against intracellular pathogens. IL-23 was critical for the expansion or maintenance of gammadelta and double negative (DN) alphabeta T cells. These cells were rapidly recruited to the site of infection and produced large amounts of IL-17, IFN-gamma, and TNF-alpha. Notably, DN T cells transferred into L. monocytogenes-infected RAG2(-/-) mice prevented bacterial growth, confirming their protective role against intracellular pathogens. Our results show that IL-23 regulates the function of IL-17-producing gammadelta and DN T cells, two essential components of the early protective immune response directed against intracellular pathogens.
Riol-Blanco
Lorena
L
Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA, USA.
Lazarevic
Vanja
V
Awasthi
Amit
A
Mitsdoerffer
Meike
M
Wilson
Brian S
BS
Croxford
Andy
A
Waisman
Ari
A
Kuchroo
Vijay K
VK
Glimcher
Laurie H
LH
Oukka
Mohamed
M
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D053760:Interleukin-23 Subunit p19 / Q000502:physiology*; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D008822:Mice, Transgenic; D010537:Peritoneum / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015704:CD4 Antigens; D016827:CD8 Antigens; C508841:Il23a protein, mouse; D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018123:Receptors, Interleukin; D014409:Tumor Necrosis Factor-alpha; C528688:interleukin-23 receptor, mouse; D007371:Interferon-gamma