Presentation is loading. Please wait.

Presentation is loading. Please wait.

Th 17 Th 1 IL-21 IL-12 TGFβ + IL-1 IFNγ RORγt T-bet IL-6 IL-23 IL-4

Published bySherilyn Doyle Modified over 8 years ago

Similar presentations

Presentation on theme: "Th 17 Th 1 IL-21 IL-12 TGFβ + IL-1 IFNγ RORγt T-bet IL-6 IL-23 IL-4"— Presentation transcript:

1

2 Th 17 Th 1 IL-21 IL-12 TGFβ + IL-1 IFNγ RORγt T-bet IL-6 IL-23 IL-4
Not produce classical Th1/Th2 cytokines Low levels GATA-3/T-bet IL-4/IFNγ supress differentiation Th 17 Th 1 IL-21 IL-12 TGFβ + IL-1 IFNγ RORγt T-bet IL-6 Naive CD4 T IL-23 IL-4 GATA-3 Foxp3 TGFβ IL-2 iTreg Th 2 IL-4 TGFβ A little history

3 IL-22 IL-2 IL-17a IFNγ Th 17 Th 1 IL-17f LTα IL-21 IL-12 TGFβ + IL-1
Extracellular bacteria Fungi Autoimmunity Intracellular pathogens Autoimmunity IL-22 IL-2 IL-17a IFNγ Th 17 Th 1 IL-17f LTα IL-21 IL-12 TGFβ + IL-1 (IL-10) IFNγ (IL-10) RORγt/Stat3 T-bet/Stat4 IL-21 IL-6 Naive CD4 T IL-23 IL-4 GATA-3/Stat5 Foxp3/Stat5 TGFβ + IL-2 IL-2 IL-13 IL-35 iTreg Th 2 IL-4 IL-10 IL-5 Immune tolerance Lymphocyte homeostasis Regulation of immune responses Extracellular pathogens Allergy and asthma Amphiregulin TGFβ IL-25 IL-10 A little history Factors of differentiation Produced cytokines Transcription factors

4 Cytokines

5 IFNγ Th 1 LTα IL-2 Intracellular pathogens (Mycobacteria) Autoimmunity
Activate macrophages to increase their microbicidal activity LTα Mediates variety of inflammatory, immunostimulatory, and antiviral responses IL-2 CD4 cell memory (critical for CD8 memory formation) The cells: cytokine produced and functions

6 IL-5 IL-13 IL-9 Th 1 IL-10 IL-4 Th 2 Amphiregulin IL-25 IL-4 IL-5
mucin Eosinophil serotonin IL-4 IL-13 TNF-α Recruits eosinophils histamine Epithelial cell lymphocyte IL-5 Expulsion of helmints Airway hypersensitivity Mast cell Mast cell Basophil IL-13 Recruits mast cells and lymphocytes Induces mucin production IL-9 FcЄRI FcЄRI Major mediator for IgE in B cells Th 1 Supression of Th1 IL-10 IL-4 Supression of dendritic cells function Dendritic cell Positive feedback for Th2 differentiation Th 2 Amphiregulin Epithelial cell Induces epithelial cells proliferation IL-25 Naive CD4 T IL-4 IL-17B CCL5 CCL11 IL-5 Extracellular pathogens (helmints) Allergy and asthma Enhances IL-4 and IL-5 production Recruits eosinophils Eosinophil

7 IL-6 IL-8 Th 17 IL-17a LCR IL-17A IL-17f IL-6/IL-23 Stat 6 IL-21 IL-22
Naive CD4 T Induction of chemokines Induction of inflammatory cytokines IL-6 IL-8 Inflammatory responses Th 17 IL-17a LCR Neutrophil Higher affinity Recruit and activate nuetrophils IL-17A IL-17f IL-6/IL-23 Stat 6 Dendritic cell CD8 T IL-21 Positive feedback amplifier Acts on CD8, B cells, NK and Dendritic cells NK IL-22 B cell Mediates dermal inflammation Prtotects hepatocytes during acute liver inflammation Mediates host defence against bacteria (Klebsiella pneumoniae and Citrobacter rodentium) Extracellular bacteria Fungi Autoimmunity The cells: cytokine produced and functions

8 IL-10 TGFβ IL-35 Treg Immune tolerance Lymphocyte homeostasis
Regulation of immune responses IL-10 Negative regulatory mechanism for limmiting immune responses to prevent host tissue damage Mediates supression in some cases Prevention and cure of inflammatory bowel disease Limits the severity of EAE (experimental autoimmune encephalomyelitis) Stimulation of protective immunity during the pathogen persistence TGFβ IL-35 Treg Supressive activity The cells: cytokine produced and functions

9 Receptors

10 ! ! Th 17 Th 1 IL-12 IFNγ IL-4 IL-2 IL-2 iTreg Th 2 IL-18Rα IL-12Rβ1
TCR activation Th 17 Th 1 IL-12 IFNγ CCR6 CCR5 CCR4 CXCR3 Naive CD4 T IL-2Rα (CD25) IL-2Rα (CD25) CTLA-4 IL-4 IL-4α IL-33Rα (T1/ST2) ! IL-2 IL-2 GITR iTreg Th 2 CD103 Folr4 CRTh2 CCR3 CCR8 CCR4 Expression of cytokine and chemokine receptors by Th cells

11 Transcriptional Factors
Transcriptional factors critical for each T helper lineage

12 Stat4 IFNγ IL-12 RORγt Runx3 Th 17 Th 1 IRF4 RORα Stat1 T-bet Stat3
Th17 differentiation Transcriptional repressor during CD8 development IFNγ IL-12 RORγt Runx3 NF-κB inducer Th 17 Th 1 IRF4 RORα Stat1 IFNγ mediated Induction of T-bet RORγt expression T-bet Stat3 Stat4 IL-21 Th1 master regulator Major signal trancducer for IL-21, IL-23, IL-21 IL-6 IL-12 signal transducer Indice IFNγ production in activated CD4 cells Naive CD4 T IL-23 Induction of IL-23R TGFβ Cytokine driven proliferation and cell survival Maintaines suppressive sctivity IL-4 IL-2 Stat5a/Stat5b Foxp3 IL-2 iTreg Th 2 Major signal trancducer during IL-4 mediated Th2 differentiation Stat6 c-Maf Stat5 Enhances IL-4 production Th2 differentiation Th2 master regulator GATA-3 Treg development Gfi-1 Foxp3 induction Modulates IL-2 signals Transcriptional factors critical for each T helper lineage

13 T helper differentiation

14 IL-12 Stat1 T-bet IFNγ IFNγ IL-12 Stat4 Th 1 IL-2 LTα IFNγ (IL-10)
Naive CD4 T Naive CD4 T Dendritic cell Naive CD4 T IL-12 Stat1 NK T-bet IFNγ Naive CD4 T Selection IFNγ IL-12Rβ2 IL-12 IL-12Rβ2 IL-12Rβ1 IL-18Rα CXCR3 CCR5 Stat4 Naive CD4 T Th 1 IL-2 LTα IFNγ (IL-10) IL-18Rα Naive CD4 T IL-12 T-bet/Stat4 Stat4 IFNγ Naive CD4 T IL-18 IL-12Rβ2 (sustains) IL-12 IFNγ IL-12Rβ2 T helper differentiation Th1 cell differentiation

15 IL-4 IL-2 Stat6 Stat6 GATA-3 Gfi-1 GATA-3 IL-4 IL-4 GATA-3 GATA-3
exogenous Naive CD4 T Stat6 Naive CD4 T Stat6 GATA-3 Gfi-1 selects Naive CD4 T Transcriptional repressor GATA-3 Naive CD4 T IL-4 IL-4 Naive CD4 T GATA-3 Naive CD4 T GATA-3 Stat5 Naive CD4 T IL-2 Th 2 IL-4α IL-2Rα (CD25) IL-33Rα (T1/ST2) CCR3 CCR4 CCR8 CRTh2 IL-4 IL-5 IL-13 IL-25 IL-10 Amphiregulin GATA-3 Va Csn Il4/Il13 Naive CD4 T Stat5 HSII HSIII T helper differentiation Th2 cell differentiation

16 IL-6 Th 17 IL-21 IL-17f IL-17a IL-22 (IL-10) TGFβ IL-21 RORγt IL-23
Cells of innate immuntiy Naive CD4 T IL-6 Th 17 IL-23R IL-18Rα IL-1R1 CCR6 CCR4 IL-21 IL-17f IL-17a IL-22 (IL-10) TGFβ Naive CD4 T IL-21 RORγt IL-23 Stat3 IL-23 IL-6 Naive CD4 T IL-21 RORγt IL-23 IL-21 T helper differentiation Th17 cell differentiation

17 TGFβ Smad3 NFAT IL-10 foxp3 IL-2 iTreg TGFβ IL-35 Foxp3 TGFβ Stat5
Naive CD4 T iTreg IL-2Rα (CD25) CTLA-4 GITR Folr4 CD103 TGFβ IL-10 IL-35 NFAT foxp3 IL-2 Naive CD4 T TGFβ Foxp3 Naive CD4 T Stat5 IL-2 T helper differentiation Treg cell differentiation

18 Cross-regulation of differentiation
Levels of cross-regulation: By cytokines Transcriptional regulation of critical factors Cytokine transcription Cross-regulation of T helper differentiation

19 Treg Th17 Th2 Th1 IL-2 IL-17 IL-4 IFNγ TGFβ RORγt Stat5 Stat4 GATA-3
T-bet Foxp3 Stat3 Gfi-1 Runx3 Cross-regulation of T helper differentiation

20 Epigenetic changes in Th differentiation

21 Epigenetic changes in Th differentiation

22 Immunologic abnormalities
Immunologic abnormalities resulting from mutations or polymorphisms in the pathways of Th differentiation

23 Th 17 Stat3 Treg Foxp3 IL2RA GATA-3 Th 2 Th 1 T-bet
Susceptibility to some bacterial infections Inability to develop Th17 Treg IPEX syndrome (immunodysregulation, polyendocrinopathy, enteropathy, x-linked) Inability to develop Treg Foxp3 IL2RA IPEX like syndrome Th 2 GATA-3 HDR syndrome (hypoparathyroidism, sensorineural deafness, renal dyplasia) Differentiation into Th2 is diminished Th 1 T-bet Asthma and airway hyperresponsiveness Immunologic abnormalities resulting from mutations or polymorphisms in the pathways of Th differentiation

24 Thank You

Download ppt "Th 17 Th 1 IL-21 IL-12 TGFβ + IL-1 IFNγ RORγt T-bet IL-6 IL-23 IL-4"

Similar presentations

The life history of T lymphocytes

The life history of T lymphocytes
José Pedro Lopes Exhausted CD3 CD8 TCR TIM3 1B11 LAG3 Generated in chronic antigen- mediated TCR stimulation. Express inhibitory receptors and lack effector.

José Pedro Lopes Exhausted CD3 CD8 TCR TIM3 1B11 LAG3 Generated in chronic antigen- mediated TCR stimulation. Express inhibitory receptors and lack effector.
Rol central de las células B en el desarrollo de daño renal autoimune.

Rol central de las células B en el desarrollo de daño renal autoimune.
Regulatory T cells. Control of potential T cell self-reactivity: tolerance Random generation of an immense T-cell repertoire (~ 10 15 different TCRs ):

Regulatory T cells. Control of potential T cell self-reactivity: tolerance Random generation of an immense T-cell repertoire (~ different TCRs ):
Cytokines and Thelper subsets MCB 150, Pr Coscoy.

Cytokines and Thelper subsets MCB 150, Pr Coscoy.
T cell ontology Penny Morel 5/13/08. General issues Introduce “thymocyte” to replace immature Make definitions more precise. DN1 thymocyte - CD4 - CD8.

T cell ontology Penny Morel 5/13/08. General issues Introduce “thymocyte” to replace immature Make definitions more precise. DN1 thymocyte - CD4 - CD8.
Immunity to microbes (mechanisms of defense against

Immunity to microbes (mechanisms of defense against
Th 细胞亚群和 T 记忆细胞 季明春 扬州大学医学院 2010-12. 2 Th 细胞亚群 Th1/Th2 cells Th17 Cells Tfh Cells Th9 Cells Treg Cells.

Th 细胞亚群和 T 记忆细胞 季明春 扬州大学医学院 Th 细胞亚群 Th1/Th2 cells Th17 Cells Tfh Cells Th9 Cells Treg Cells.
Effector T-cells, effector T-cell functions. Activation of effector T-cells is less dependent on co-receptor signaling Naive or „resting” T cells… relentless.

Effector T-cells, effector T-cell functions. Activation of effector T-cells is less dependent on co-receptor signaling Naive or „resting” T cells… relentless.
T-CELL DIFFERENTIATION IN THE PERIPHERY

T-CELL DIFFERENTIATION IN THE PERIPHERY
Defenses Against Infection 1. Innate responses (humoral and cellular) 2. Immunity to intracellular pathogens NK cells, control of Th1/Th2 responses 3.

Defenses Against Infection 1. Innate responses (humoral and cellular) 2. Immunity to intracellular pathogens NK cells, control of Th1/Th2 responses 3.
T cell & Rui He Department of Immunology Shanghai Medical School Fudan University T cell-mediated immunity.

T cell & Rui He Department of Immunology Shanghai Medical School Fudan University T cell-mediated immunity.
Efector functions of CD4 + and CD8 + T-cells. Naivna CD4 + T Naive CD4 + T Th1 Th2 Th17 Defense- intracellular pathogens, stimulation of IgG production.

Efector functions of CD4 + and CD8 + T-cells. Naivna CD4 + T Naive CD4 + T Th1 Th2 Th17 Defense- intracellular pathogens, stimulation of IgG production.
Induction of adaptive immunity Differentiation of Th Cytokines Cell-mediated immunity Humoral immunity Immunological memory Immune effector function.

Induction of adaptive immunity Differentiation of Th Cytokines Cell-mediated immunity Humoral immunity Immunological memory Immune effector function.
Cytokines Non-antibody proteins acting as mediators between cells, termed: Monokines – mononuclear phagocytes Lymphokines – activated T cells, especially.

Cytokines Non-antibody proteins acting as mediators between cells, termed: Monokines – mononuclear phagocytes Lymphokines – activated T cells, especially.
Functions Receptors Signaling Chapter 11

Functions Receptors Signaling Chapter 11
Introduction to Autoimmunity Alon Monsonego, Ph.D. The department of Microbiology and Immunology Tel: 08-647-9052.

Introduction to Autoimmunity Alon Monsonego, Ph.D. The department of Microbiology and Immunology Tel:
Tolerance, autoimmunity and the pathogenesis of immune-mediated inflammatory diseases Abul K. Abbas UCSF.

Tolerance, autoimmunity and the pathogenesis of immune-mediated inflammatory diseases Abul K. Abbas UCSF.
Cytokines and Chemokines Chapter 12 Karl A. Brokstad 1.

Cytokines and Chemokines Chapter 12 Karl A. Brokstad 1.
A a Activated T-cell Mature naive T-cell Memory T-cell T-CELL DIFFERENTIATION IN THE PERIPHERY Ag CD4 TCR APC CD8 TCR APC CD4 TCR APC CD8 TCR APC CD4 TCR.

A a Activated T-cell Mature naive T-cell Memory T-cell T-CELL DIFFERENTIATION IN THE PERIPHERY Ag CD4 TCR APC CD8 TCR APC CD4 TCR APC CD8 TCR APC CD4 TCR.

Similar presentations

Ads by Google