Perturbed thymopoiesis in vitro in the absence of suppressor of cytokine signalling 1 and 3.
Cytokine signals are central to the differentiation of thymocytes and their stepwise progression through defined developmental stages. The intensity and duration of cytokine signals are regulated by the suppressor of cytokine signalling (SOCS) proteins. A clear role for SOCS1 during the later stages of thymopoiesis has been established, but little is known about its role during early thymopoiesis, nor the function of its closest relative, SOCS3. Here, we find that both SOCS1 and SOCS3 are expressed during early thymopoiesis, with expression coincident during the double negative (DN)2 and DN3 stages. We examined thymocyte differentiation in vitro by co-culture of SOCS-deficient bone marrow cells with OP9 cells expressing the Notch ligand Delta-like1 (OP9-DL1). Cells lacking SOCS1 were retarded at the DN3:DN4 transition and appeared unable to differentiate into double positive (DP) thymocytes. Cells lacking both SOCS1 and SOCS3 were more severely affected, and displayed an earlier block in T cell differentiation at DN2, the stage at which expression of SOCS1 and SOCS3 coincides. This indicates that, in addition to their specific roles, SOCS1 and SOCS3 share overlapping roles during thymopoiesis. This is the first demonstration of functional redundancy within the SOCS family, and has uncovered a vital role for SOCS1 and SOCS3 during two important checkpoints in early T cell development.
Croom
Hayley A
HA
Signal Transduction Laboratory, St Vincent's Institute, 9 Princes Street, Fitzroy, Victoria 3065, Australia.
Izon
David J
DJ
Chong
Mark M
MM
Curtis
David J
DJ
Roberts
Andrew W
AW
Kay
Thomas W H
TW
Hilton
Douglas J
DJ
Alexander
Warren S
WS
Starr
Robyn
R
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D018920:Coculture Techniques; D005434:Flow Cytometry; D008221:Lymphoid Tissue / Q000166:cytology; D051379:Mice; D013234:Stem Cells / Q000166:cytology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000172:deficiency*; D013950:Thymus Gland / Q000166:cytology*
C491590:Socs1 protein, mouse; C491411:Socs3 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins