Marked induction of the helix-loop-helix protein Id3 promotes the gammadelta T cell fate and renders their functional maturation Notch independent.
alphabeta and gammadelta T cells arise from a common thymocyte progenitor during development in the thymus. Emerging evidence suggests that the pre-T cell receptor (pre-TCR) and gammadelta T cell receptor (gammadeltaTCR) play instructional roles in specifying the alphabeta and gammadelta T-lineage fates, respectively. Nevertheless, the signaling pathways differentially engaged to specify fate and promote the development of these lineages remain poorly understood. Here, we show that differential activation of the extracellular signal-related kinase (ERK)-early growth response gene (Egr)-inhibitor of DNA binding 3 (Id3) pathway plays a defining role in this process. In particular, Id3 expression served to regulate adoption of the gammadelta fate. Moreover, Id3 was both necessary and sufficient to enable gammadelta-lineage cells to differentiate independently of Notch signaling and become competent IFNgamma-producing effectors. Taken together, these findings identify Id3 as a central player that controls both adoption of the gammadelta fate and its maturation in the thymus.
Lauritsen
Jens Peter Holst
JP
Blood Cell Development and Cancer Keystone, Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, Philadelphia, PA 19111-2497, USA.
Wong
Gladys W
GW
Lee
Sang-Yun
SY
Lefebvre
Juliette M
JM
Ciofani
Maria
M
Rhodes
Michele
M
Kappes
Dietmar J
DJ
Zúñiga-Pflücker
Juan Carlos
JC
Wiest
David L
DL
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D051766:Early Growth Response Protein 1 / Q000276:immunology / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020710:RGS Proteins / Q000276:immunology / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D051880:Receptors, Notch / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology
D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D051796:Inhibitor of Differentiation Proteins; D020710:RGS Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D051880:Receptors, Notch; C488188:Rgs1 protein, mouse; C067679:Idb3 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases