T-lineage cells require the thymus but not VDJ recombination to produce IL-17A and regulate granulopoiesis in vivo.
IL-17A and IL-17F regulate granulopoiesis and are produced by memory T cells. Rag1(-/-) recombinase-activating gene-deficient mice cannot produce mature T cells but maintain normal neutrophil counts. Athymic nude mice are neutropenic or have near-normal neutrophil counts, depending on the prevailing intestinal flora, and do not produce IL-17A. By contrast, thymi from Rag1(-/-) mice contain as much IL-17A as those from wild-type (WT) mice. IL-17A-producing cells are found in the double negative DN1 compartment of the Rag1(-/-) thymus and express intracellular CD3. These cells colonize the spleen and mesenteric lymph node and secrete IL-17A in vitro following stimulation with IL-23 at a level similar to that of WT splenocytes. Adoptively transferred Rag1(-/-) or WT thymocytes correct neutrophil counts in neutropenic nude mice. We conclude that the development of IL-17A-producing T-lineage cells requires an intact thymic epithelium, but not V(D)J recombination.
Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA.
Emily
E
Smith
Sibylle
S
von Vietinghoff
Matthew A
MA
Stark
Alexander
A
Zarbock
John M
JM
Sanders
Amanda
A
Duley
Jesus
J
Rivera-Nieves
Timothy P
TP
Bender
Klaus
K
Ley
D000818:Animals; D000916:Antibody Diversity / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D015329:Gene Rearrangement, T-Lymphocyte / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D007133:Immunoglobulin Joining Region / Q000235:genetics / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D008822:Mice, Transgenic; D009503:Neutropenia / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
C098680:Il17a protein, mouse; D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D020381:Interleukin-17; D011948:Receptors, Antigen, T-Cell