James I Kim, I-Cheng Ho, Michael J Grusby, Laurie H Glimcher  Immunity 

Slides:



Advertisements
Similar presentations
Volume 6, Issue 5, Pages (November 2004)
Advertisements

Cheng-Ming Sun, Edith Deriaud, Claude Leclerc, Richard Lo-Man  Immunity 
Volume 16, Issue 6, Pages (June 2002)
Hematopoietic progenitor kinase 1 supports apoptosis of T lymphocytes
Takashi Tanaka, Michelle A. Soriano, Michael J. Grusby  Immunity 
by Alexander Kiani, Francisco J
Macrophages from C3-deficient mice have impaired potency to stimulate alloreactive T cells by Wuding Zhou, Hetal Patel, Ke Li, Qi Peng, Marie-Bernadette.
Inhibition of Th1 Differentiation by IL-6 Is Mediated by SOCS1
Elisabeth Roesler, MSc, Richard Weiss, PhD, Esther E
Wei Hu, Ty Dale Troutman, Ramakrishna Edukulla, Chandrashekhar Pasare 
Ann M. Ranger, Mohamed Oukka, Jyothi Rengarajan, Laurie H. Glimcher 
Volume 31, Issue 2, Pages (August 2009)
Volume 117, Issue 5, Pages (November 1999)
Volume 124, Issue 7, Pages (June 2003)
Volume 6, Issue 2, Pages (February 1997)
Biochemical Mechanisms of IL-2–Regulated Fas-Mediated T Cell Apoptosis
ROG, Repressor of GATA, Regulates the Expression of Cytokine Genes
Volume 15, Issue 1, Pages (July 2001)
Durbaka V.R Prasad, Sabrina Richards, Xoi Muoi Mai, Chen Dong  Immunity 
Volume 11, Issue 4, Pages (October 1999)
Volume 18, Issue 5, Pages (May 2003)
Volume 26, Issue 2, Pages (February 2007)
I-Cheng Ho, Martin R Hodge, John W Rooney, Laurie H Glimcher  Cell 
Volume 87, Issue 2, Pages (February 2015)
Volume 11, Issue 5, Pages (November 1999)
Volume 21, Issue 5, Pages (November 2004)
IGF-II-Mediated COX-2 Gene Expression in Human Keratinocytes Through Extracellular Signal-Regulated Kinase Pathway  Hye Jung Kim, Tae-Yoon Kim  Journal.
Volume 4, Issue 4, Pages (October 2008)
Yongli Bai, Chun Yang, Kathrin Hu, Chris Elly, Yun-Cai Liu 
Mark H Kaplan, Ulrike Schindler, Stephen T Smiley, Michael J Grusby 
Volume 21, Issue 2, Pages (August 2004)
Impaired Development of Th2 Cells in IL-13-Deficient Mice
MUC1 Oncoprotein Stabilizes and Activates Estrogen Receptor α
Impaired Th2 Subset Development in the Absence of CD4
Volume 8, Issue 6, Pages (June 1998)
Volume 34, Issue 1, Pages (January 2011)
Down-Regulation of IL-4 Gene Transcription and Control of Th2 Cell Differentiation by a Mechanism Involving NFAT1  Alexander Kiani, João P.B Viola, Andrew.
Defective NK Cell Activity and Th1 Response in IL-18–Deficient Mice
Stanford L Peng, Andrea J Gerth, Ann M Ranger, Laurie H Glimcher 
MUC1 Oncoprotein Stabilizes and Activates Estrogen Receptor α
Volume 4, Issue 4, Pages (April 1996)
Volume 29, Issue 1, Pages (July 2008)
Volume 33, Issue 4, Pages (October 2010)
Mukesh Kumar, PhDa, Aruna K. Behera, PhDa, Jianan Hu, MDa, Richard F
Volume 29, Issue 6, Pages (December 2008)
IgH Class Switch Recombination to IgG1 in DNA-PKcs-Deficient B Cells
ROG, Repressor of GATA, Regulates the Expression of Cytokine Genes
Impaired Development of Th2 Cells in IL-13-Deficient Mice
Volume 15, Issue 4, Pages (August 2004)
Volume 21, Issue 2, Pages (August 2004)
Volume 9, Issue 5, Pages (November 1998)
Volume 16, Issue 6, Pages (June 2002)
Andrew T Miller, Heather M Wilcox, Zhongbin Lai, Leslie J Berg 
Volume 15, Issue 2, Pages (August 2001)
Silva H Hanissian, Raif S Geha  Immunity 
Volume 34, Issue 5, Pages (May 2011)
Volume 6, Issue 6, Pages (June 1997)
Targeted Cleavage of Signaling Proteins by Caspase 3 Inhibits T Cell Receptor Signaling in Anergic T Cells  Irene Puga, Anjana Rao, Fernando Macian  Immunity 
Volume 11, Issue 3, Pages (September 1999)
Volume 28, Issue 1, Pages (January 2008)
Notch 1 Signaling Regulates Peripheral T Cell Activation
Toll-Dependent Control Mechanisms of CD4 T Cell Activation
Volume 9, Issue 3, Pages (September 1998)
Volume 31, Issue 6, Pages (December 2009)
PU.1 Expression Delineates Heterogeneity in Primary Th2 Cells
Volume 24, Issue 1, Pages (January 2006)
Volume 28, Issue 1, Pages (January 2008)
Volume 24, Issue 6, Pages (June 2006)
Regulation of the Th2 Cytokine Locus by a Locus Control Region
Volume 10, Issue 3, Pages (March 1999)
Presentation transcript:

The Transcription Factor c-Maf Controls the Production of Interleukin-4 but Not Other Th2 Cytokines  James I Kim, I-Cheng Ho, Michael J Grusby, Laurie H Glimcher  Immunity  Volume 10, Issue 6, Pages 745-751 (June 1999) DOI: 10.1016/S1074-7613(00)80073-4

Figure 1 Impaired Production of IL-4 in c-maf−/− Mice Impaired production of IL-4 in unskewed (left panels) and in Th2-skewed (right panels) conditions upon secondary stimulation of c-maf−/− spleen cells from (A) whole splenocytes and (B) purified naive CD4+ T cells. For unskewed conditions, freshly isolated splenocytes from wild-type or c-maf−/− mice were cultured at 2 × 106 cells/ml with 1 μg/ml of plate-bound anti-CD3 for 7 days, washed, and restimulated for 48 hr with anti-CD3. For Th2-skewed conditions, cells were stimulated in the presence of exogenous IL-4 during the 7 day incubation. IL-4 was measured by ELISA in supernatants taken at 48 hr. Naive CD4+ T cells were isolated by CD4 FITC/MEL-14 PE antibody staining and MoFlo purification. Immunity 1999 10, 745-751DOI: (10.1016/S1074-7613(00)80073-4)

Figure 2 Decreased Production of IL-4 in NK T Cells c-maf−/− or wt littermates were injected i.v. with PBS or 4 μg of anti-CD3. Total cellular RNA (10 μg) prepared from spleens was fractionated in 1.2% agarose gels, blotted onto nylon membranes, and hybridized. Hybridization to an IL-4 cDNA probe revealed impaired induction of transcripts encoding IL-4 in c-maf−/− spleen cells. Filters were stripped and rehybridized with a γ-actin cDNA probe to control for amount of RNA loaded per lane. IL-4 film and γ-actin film were exposed for 12 hr and 1 hr, respectively. Densitometry shows a 2× to 4× decrease in −/− lanes when normalized for loading. Immunity 1999 10, 745-751DOI: (10.1016/S1074-7613(00)80073-4)

Figure 3 Defective Production of Other Th2 Cytokines in c-maf−/− Mice in Unskewed Conditions Is Restored by Addition of Exogenous IL-4 Supernatants from differentiated cultures of (A) whole splenocytes or (B) purified naive CD4+ T cells under unskewed (left panels) and in Th2-skewed (right panels) conditions upon secondary stimulation were analyzed by ELISA. Mean level of cytokine production is shown as a horizontal bar. IL-13 was not detected in any of the supernatants of the purified naive cells. Five wt mice were analyzed for (A) and two wt mice for (B). The closed bars represent wt mice, and the open bars represent c-maf−/− mice. Immunity 1999 10, 745-751DOI: (10.1016/S1074-7613(00)80073-4)

Figure 4 c-Maf Does Not Transactivate the IL-5 or IL-10 Promoters M12 cells were cotransfected with luciferase reporter plasmids, driven by IL-5 (IL-5 Luc), IL-10 (IL-10 Luc), or IL-4 (IL-4 Luc) promoters, together with a c-Maf expression vector (c-Maf) or the control empty expression vector (vector). Promoter activity was quantitated by luciferase assay 24 hr post transfection. The promoter-luciferase activity observed by transfection of the empty expression vector was normalized to 1. Immunity 1999 10, 745-751DOI: (10.1016/S1074-7613(00)80073-4)

Figure 5 Diminished IgG1 and IgG2a and Normal IgE Antibody Responses in c-maf−/− Mice Mice were immunized with DNP-OVA in complete Freund’s adjuvant and levels of OVA-specific Ig quantitated by ELISA 14 days later (Kaplan et al. 1996). Horizontal bars indicate mean values. Immunity 1999 10, 745-751DOI: (10.1016/S1074-7613(00)80073-4)