醫(yī)學(xué)免疫學(xué)課件：IgE-FcεR Signaling in Immune Response

1、IgE-FcR Signaling in Immune ResponseManikandan, J., et al., Deciphering the structure and function of FcepsilonRI/mast cell axis in the regulation of allergy and anaphylaxis: a functional genomics paradigm. Cell Mol Life Sci, 2012. 69(12): p. 1917-29.Overview of IgE-FcR signaling IgE-FcR interaction

2、 1.1 FcRI 1.2 IgE-FcRI interaction 1.3 CD23 (FcRII) 1.4 IgE-CD23 interaction 2. FcR mediated signaling 2.1 FcRI mediated signaling 2.2 CD23 mediated signaling3. Advance in FcR mediated signaling ContentIgE-FcR interaction 2-MC, basophilFcRI2-DC, eosinophil ASM, IECCD23-B, T, DC, eosinophil, platelet

3、Sutton, B.J. and A.M. Davies, Structure and dynamics of IgE-receptor interactions: FcepsilonRI and CD23/FcepsilonRII. Immunol Rev, 2015. 268(1): p. 222-35.CD23(FcRII)FcR2sFceRIFcRIIgE-FcR interaction Sutton, B.J. and A.M. Davies, Structure and dynamics of IgE-receptor interactions: FcepsilonRI and C

4、D23/FcepsilonRII. Immunol Rev, 2015. 268(1): p. 222-35.ITAMIgE-FcRI interaction IgEIgE-FcR interaction Sutton, B.J. and A.M. Davies, Structure and dynamics of IgE-receptor interactions: FcepsilonRI and CD23/FcepsilonRII. Immunol Rev, 2015. 268(1): p. 222-35.CD23 (FcRII) IgE-FcR interaction Sutton, B

5、.J. and A.M. Davies, Structure and dynamics of IgE-receptor interactions: FcepsilonRI and CD23/FcepsilonRII. Immunol Rev, 2015. 268(1): p. 222-35.IgE-CD23 interactionSutton, B.J. and A.M. Davies, Structure and dynamics of IgE-receptor interactions: FcepsilonRI and CD23/FcepsilonRII. Immunol Rev, 201

6、5. 268(1): p. 222-35.IgE-FcR interaction Ca2+IgE-FcR interaction Sutton, B.J. and A.M. Davies, Structure and dynamics of IgE-receptor interactions: FcepsilonRI and CD23/FcepsilonRII. Immunol Rev, 2015. 268(1): p. 222-35.IgE-sCD23 interactionFcR mediated signaling FcRI mediated signalingCD23(FcRII) m

7、ediated signalingFcR mediated signaling Wu, L.C., Immunoglobulin E receptor signaling and asthma. J Biol Chem, 2011. 286(38): p. 32891-7. Abramson, J. and I. Pecht, Regulation of the mast cell response to the type 1 Fc epsilon receptor. Immunol Rev, 2007. 217: p. 231-54.ActivationInhibitionProtein t

8、yrosine kinaseLyn, Syk, Fyn, Hck, FgrCsk, BtkAdaptor proteinLAT, NTALDok-1PhosphatasePI3K, PLC-SHIP, SHP-1/2, PTP- FcRI mediated signalingWu, L.C., Immunoglobulin E receptor signaling and asthma. J Biol Chem, 2011. 286(38): p. 32891-7.FcR mediated signaling FcRI mediated activation signalingFcR medi

9、ated signaling FcRI mediated activation signalingWu, L.C., Immunoglobulin E receptor signaling and asthma. J Biol Chem, 2011. 286(38): p. 32891-7. Abramson, J. and I. Pecht, Regulation of the mast cell response to the type 1 Fc epsilon receptor. Immunol Rev, 2007. 217: p. 231-54.SykLAT(NTAL)PLC-IP3C

10、a2+ degranulationFyn PI3K PIP3 Sphk S1P Ca2+ degranulationSyk LATPLC- p38, Jnk, Erk, NF-B transcriptionFyn PI3K Akt mTOR transcriptionHck, FgrWu, L.C., Immunoglobulin E receptor signaling and asthma. J Biol Chem, 2011. 286(38): p. 32891-7.FcR mediated signaling FcRI mediated activation signalingSykL

11、AT(NTAL)PLC-IP3Ca2+ degranulationWu, L.C., Immunoglobulin E receptor signaling and asthma. J Biol Chem, 2011. 286(38): p. 32891-7.FcR mediated signaling FcRI mediated activation signalingFyn PI3K PIP3 Sphk S1P Ca2+ degranulationWu, L.C., Immunoglobulin E receptor signaling and asthma. J Biol Chem, 2

12、011. 286(38): p. 32891-7.FcR mediated signaling FcRI mediated activation signalingSyk LATPLC- p38, Jnk, Erk, NF-B transcriptionWu, L.C., Immunoglobulin E receptor signaling and asthma. J Biol Chem, 2011. 286(38): p. 32891-7.FcR mediated signaling FcRI mediated activation signalingFyn PI3K Akt mTOR t

13、ranscriptionSibilano, R., B. Frossi and C.E. Pucillo, Mast cell activation: a complex interplay of positive and negative signaling pathways. Eur J Immunol, 2014. 44(9): p. 2558-66.Hck, FgrFcR mediated signaling FcRI mediated activation signalingFcR mediated signaling Negative Regulators of FcRI Sign

14、alingIntracellular protein -PTK: Csk, Btk -Adaptor protein: Dok-1 -Phosphatase: SHIP, SHP-1/2, PTP- Surface protein -ITIM containing receptors, FcRIIB -TLR4 -TRPM4Wu, L.C., Immunoglobulin E receptor signaling and asthma. J Biol Chem, 2011. 286(38): p. 32891-7.Wu, L.C., Immunoglobulin E receptor sign

15、aling and asthma. J Biol Chem, 2011. 286(38): p. 32891-7.FcR mediated signaling Negative Regulators of FcRI SignalingSibilano, R., B. Frossi and C.E. Pucillo, Mast cell activation: a complex interplay of positive and negative signaling pathways. Eur J Immunol, 2014. 44(9): p. 2558-66.FcR mediated si

16、gnaling Negative Regulators of FcRI SignalingKey mediators of FceRIManikandan, J., et al., Deciphering the structure and function of FcepsilonRI/mast cell axis in the regulation of allergy and anaphylaxis: a functional genomics paradigm. Cell Mol Life Sci, 2012. 69(12): p. 1917-29.FcR mediated signa

17、ling FcRI signaling-DCShin, J.S. and A.M. Greer, The role of FcepsilonRI expressed in dendritic cells and monocytes. Cell Mol Life Sci, 2015. 72(12): p. 2349-60.FcR mediated signaling (a) IgE clearance(b) T cell tolerance(c) Pro- or anti-imflammationKelly, B.T. and M.H. Grayson, Immunoglobulin E, wh

18、at is it good for? Ann Allergy Asthma Immunol, 2016. 116(3): p. 183-7.Acharya, M., et al., CD23/FcepsilonRII: molecular multi-tasking. Clin Exp Immunol, 2010. 162(1): p. 12-23.CD23 mediated signalingFcR mediated signaling B cell -IgE synthesis -Antigen processingIEC -TranscytosisAdvance in FcR media

19、ted signalingNovel molecules and mechanismDisease-relatedTherapy-relatedNovel molecules and mechanismAdvance in FcR mediated signalingCD23FcRI -Novel molecules Positive: Tim-3, ORMDL3, Notch, STAT5-GATA2 Negative: galectin-3,Ehf, CD151, adenine, CD72, Tespa1, miRNA -Novel mechanism Circadian clock S

20、ex hormonesdegranulation Acidic environmentIL-6, IL-13Disease-relatedAdvance in FcR mediated signalingNoxious substances, eg. snake venom toxicityNK cells lacking FcRHCVLin- CD34hi CD117 int/hi FcRI+ cellsasthmaFcR deficiencyobesity and glucose toleranceCD23 transcytosisinflammation and asthmaTherapy-relatedAdvance in FcR mediated signalingOmalizumab（奧馬珠單抗）|histamineCTLA4FcR|CD23Resveratrol（白藜蘆醇）|MAPKSutton, B