Naive CD4 lymphocytes undergo a polarization process in the periphery to become induced Th17 (iTh17) cells. Using retinoic acid-related orphan receptor γt (RORγt)-gfp mice, we found that RORγt and the transcription factor promyelocytic leukemia zinc finger (PLZF) are valuable new markers to identify the recently described natural Th17 (nTh17) cell population. nTh17 cells are thymically committe...

Neuronal differentiation is regulated by proneural genes that promote neurogenesis and inhibitory mechanisms that maintain progenitors. This raises the question of how the up-regulation of proneural genes required to initiate neurogenesis occurs in the presence of such inhibition. We carried out loss and gain of gene function, an interaction screen for binding partners, and biochemical analyses...

Disease outcome is known to be influenced by defined subsets of invariant NKT (iNKT) cells residing in distinct locations within peripheral tissue. However, the factors governing the development of these unique iNKT sublineages during thymic development are unknown. In this study we explored the mechanism by which E protein transcription factors and their negative regulators, the Id proteins, c...

Cells δ γ Innate NKT + 6.3 δ 1V γ Development of V A large fraction of innate NKTgd T cells uses TCRs composed of a semi-invariant Vd6.3/6.4-Dd2-Jd1 chain together with more diverse Vg1-Jg4 chains. To address the role of gdTCR specificity in their generation, we analyzed their development in mice transgenic (Tg) for a Vg1-Jg4 chain frequently expressed by NKTgd cells (Tg-g) and in mice Tg for t...

The mammalian target of rapamycin (mTOR) senses and incorporates different environmental cues via the two signaling complexes mTOR complex 1 (mTORC1) and mTORC2. As a result, mTOR controls cell growth and survival, and also shapes different effector functions of the cells including immune cells such as T cells. We demonstrate in this article that invariant NKT (iNKT) cell development is control...

Fusion proteins of retinoic acid receptor ! (RAR!) with promyelocytic leukemia protein (PML-RAR!) or with promyelocytic leukemia zinc finger protein (PLZFRAR!) are associated with and likely responsible for the development of acute promyelocytic leukemia. These oncoproteins retain the ability to bind DNA and retinoic acid through the RAR! moiety. This enables them to repress RAR! target genes i...

Molecular detection of minimal residual disease (MRD) has become established to assess remission status and guide therapy in patients with ProMyelocytic Leukemia-RARA+ acute promyelocytic leukemia (APL). However, there are few data on tracking disease response in patients with rarer retinoid resistant subtypes of APL, characterized by PLZF-RARA and STAT5b-RARA. Despite their rarity (<1% of APL)...