IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways
- Liang Zhou, I. Ivanov, D. Littman
- Biology, MedicineNature Immunology
- 1 September 2007
IL-6 orchestrates a series of 'downstream' cytokine-dependent signaling pathways that, in concert with TGF-β, amplify RORγt-dependent differentiation of TH-17 cells.
Jaks and STATs: biological implications.
- W. Leonard, J. O’Shea
- BiologyAnnual Review of Immunology
- 1998
The Jak-STAT pathway is the focus of this chapter, a novel mechanism in which cytosolic latent transcription factors, known as signal transducers and activators of transcription (STATs), are tyrosine phosphorylated by Janus family tyrosin kinases (Jaks), allowing STAT protein dimerization and nuclear translocation.
A Critical Role for IL-21 in Regulating Immunoglobulin Production
- K. Ozaki, R. Spolski, W. Leonard
- Biology, MedicineScience
- 22 November 2002
It is demonstrated that, although mice deficient in the receptor for IL-21 (IL-21R) have normal lymphoid development, after immunization, these animals have higher production of the immunoglobulin IgE, but lower IgG1, than wild-type animals, suggesting that these γc-dependent cytokines may be those whose inactivation is primarily responsible for the B cell defect in humans with XSCID.
Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function
- R. Zeng, Rosanne Spolski, W. Leonard
- Biology, MedicineJournal of Experimental Medicine
- 3 January 2005
In vivo administration of IL-21 in combination with IL-15 boosted antigen-specific CD8+ T cell numbers and resulted in a cooperative effect on tumor regression, with apparent cures of large, established B16 melanomas.
Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy.
- W. Liao, Jianxin Lin, W. Leonard
- Biology, MedicineImmunity
- 24 January 2013
Interleukin-21: basic biology and implications for cancer and autoimmunity.
- R. Spolski, W. Leonard
- Biology, MedicineAnnual Review of Immunology
- 27 March 2008
The key to harnessing the power of IL-21 will depend on better understanding its range of biological actions, its mechanism of action, and the molecular basis of regulation of expression ofIL-21 and its receptor.
IL-21 Induces Differentiation of Human Naive and Memory B Cells into Antibody-Secreting Plasma Cells1
- R. Ettinger, G. Sims, P. Lipsky
- Biology, MedicineJournal of Immunology
- 15 December 2005
The data show that IL-21 plays a central role in CSR and plasma cell differentiation during T cell-dependent B cell responses and was more potent than the combination of IL-2 and IL-10.
CREB/ATF-dependent T cell receptor–induced FoxP3 gene expression: a role for DNA methylation
- Hyoung-Pyo Kim, W. Leonard
- BiologyJournal of Experimental Medicine
- 1 July 2007
This work has identified a T cell receptor–responsive enhancer in the FoxP3 first intron that is dependent on a cyclic-AMP response element binding protein (CREB)/activating transcription factor (ATF) site overlapping a CpG island that inversely correlates with CREB binding andFoxP3 expression.
Regulatory B Cells Control T Cell Autoimmunity Through IL-21-Dependent Cognate Interactions
- A. Yoshizaki, T. Miyagaki, T. Tedder
- Biology, MedicineNature
- 16 August 2012
It is shown that B10-cell maturation into functional IL-10-secreting effector cells that inhibit in vivo autoimmune disease requires IL-21 and CD40-dependent cognate interactions with T cells, and that the ex vivo expansion and reinfusion of autologous B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies.
The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue–resident regulatory T cells
- Ajithkumar Vasanthakumar, K. Moro, A. Kallies
- BiologyNature Immunology
- 1 March 2015
It is shown that interleukin 33 (IL-33) signaling through the IL-33 receptor ST2 and myeloid differentiation factor MyD88 is essential for development and maintenance of VAT-Treg cells and sustains their transcriptional signature.
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