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Home » NEI Laboratories » Laboratory of Immunology » Molecular Immunology Section

Molecular Immunology Section

Dr. Egwuagu
Dr. Egwuagu received his Ph.D from Yale University and M.P.H from Yale School of Medicine in 1987. He completed a 3- year Research Fellowship at NIH (1990). Served as a Commissioned Officer of the United States Public Health Service from 1990 and left the PHS in 2000 after promotion to the rank of Captain (06). He became a Senior Investigator in the Laboratory of Immunology in 1999 and has been the Chief, Section on Molecular Immunology since 2000.

Research:

Overall thrust of research in the Section on Molecular Immunology is governed, to a large extent, by a fervent belief that most infectious and chronic diseases of the eye and other organ systems result from inability of the host to mount an adequate immune response or because of an exuberant and over-reactive immune system. Consequently, our work has focused on understanding molecular and cellular mechanisms that regulate immune responses in the eye, with particular emphasis on the roles played by proinflammatory and anti-inflammatory cytokines elaborated by armed effector T lymphocytes.

Research activities have focused on: (i) activation and regulation of cytokine signals in resident ocular cells and inflammatory cells that mediate ocular diseases; (ii) understanding mechanisms that underlie susceptibility to intraocular inflammatory diseases (uveitis). These investigations have been carried out in cell lines or primary cells and validated in transgenic mouse and rat models.

Major Areas of Investigation and Findings:

(1) Cytokine signaling and regulation of immune homeostasis
We seek to understand negative feedback mechanisms that regulate activities of proinflammatory cytokines in the eye and how crosstalk between the plethora of cytokines that converge on uveitogenic lymphocytes and resident ocular cells is coordinated. Particular attention is given to a family of intracellular regulatory proteins called SOCS (suppressors of cytokine signaling). These proteins regulate the intensity and duration of cytokine signals. They are potential targets for immune-modulation therapy and may have neuroprotective functions in the retina.

Major findings:

(2) Role of Interferon-gamma in inflammatory and degenerative diseases of the eye
Interferon-g (IFNg) has been implicated in the immunopathogenic mechanisms of several organ-specific autoimmune diseases. Because this proinflammatory cytokine plays a central role in immunopathogenic mechanisms of ocular diseases of infectious or putative autoimmune etiology, we have used IFNg as a paradigm for understanding effects of cytokines in the eye and ocular diseases. Our investigations have focused on positive regulatory transcription factors activated by IFNg signaling pathways, with the goal of understanding pathophysiological consequences of prolonged secretion of IFNg in the eye, as occurs during chronic intraocular infections. Particular interest is on potential role of proinflammatory cytokines in retinal degenerative diseases.

Major findings:

(3) Identification of biological markers of susceptibility to uveitis
An important and unresolved issue in autoimmunity relates to the definition of risk factors for development of an organ-specific autoimmune disease. Why are some individuals resistant while others are susceptible to an organ-specific autoimmune disease? We have addressed these issues by studying molecular basis of susceptibility to experimental autoimmune uveitis (EAU), an animal model of human uveitis.

Major Finding:

The degree of susceptibility to autoimmune disease depends on the relative amounts of the antigens present in the thymus, suggesting that resistance to an organ-specific autoimmune disease may be regulated at least in part by the capacity of the host to establish central tolerance to the relevant autoantigen.

(J. Immunol.-Cutting Edge-159: 3109-3112 PubMed; Int. Rev. Immunol. 21:89-100 PubMed ; Int. Immunol. 17:1131-40 PubMed ).

Staff:

Name Title E-mail
Charles E. Egwuagu, MPH, PhD.
PubMed Aurhor Search		 Section Head Egwuaguc@nei.nih.gov
Cheng-Rong Yu, MD, PhD Staff Scientist YuC@NEI.NIH.GOV
Xuebin Liu, MD, PhD Senior Biologist liuxue@nei.nih.gov
Ahjoku Amadi-Obi, MD, FRCS Post-Doctoral Fellow ahjokua@nei.nih.gov
Yunsang Lee, PhD Post-Doctoral Fellow leeyunsa@nei.nih.gov
Allen Zhang Student allbot21887@msn.com
Rashid M. Mahdi Biologist MahdiR@NEI.NIH.GOV

View photos of the staff.

Selected Publications:

Immune Regulation

Egwuagu C.E., R-C. Yu, M. Zhang, R. M. Mahdi, S. J. Kim and I. Gery. Suppressors of Cytokine Signaling (SOCS) Proteins are Constitutively and Differentially Expressed in Th1 and Th2 Cells: Implications for Th Cell Lineage Commitment and Maintenance. (J Immunol. 168:3181, 2002). PubMed

Yu CR, Mahdi RM, Ebong S, Vistica BP, Gery I, Egwuagu CE. Suppressor of cytokine signaling 3 regulates proliferation and activation of T-helper cells. (J Biol. Chem. 278:29752, 2003).PubMed

Yu CR, Mahdi RM, Ebong S, Vistica BP, Chen J, Guo Y, Gery I and Egwuagu CE. Proliferation and STAT6 Signaling Pathways are Negatively Regulated in T-helper Cells by STAT1 and Suppressors of Cytokine Signaling (SOCS). (J. Immunol. 173-737-746, 2004).PubMed

Jackson SH, Yu CR, Mahdi RM, Ebong S, Egwuagu CE. Dendritic cell maturation requires STAT1 and is under feedback regulation by suppressors of cytokine signaling. (J Immunol. 172:2307-15, 2004).PubMed

Cytokine Signaling in the Eye

Egwuagu C.E.,Sztein J., Chan C.C., Reid W., Mahdi R., Nussenblatt R.B. and Chepelinsky A.B. Gamma Interferon Expression Disrupts Lens and Retinal Differentiation in Transgenic Mice. (Developmental Biology 166:557-568, 1994).PubMed

Egwuagu C.E.,Sztein J., Chan C.C., Reid W., Mahdi R., Nussenblatt R.B. and Chepelinsky A.B. Ectopic Expression of Gamma Interferon in The Eyes Of Transgenic Mice Induces Ocular Pathology and MHC Class II Gene Expression. (Invest. Opthalmol. Vis. Sci. 35:332-341, 1994).PubMed

Li, W., Nagineni, C.N., Ohtaka-Marayuma, C., Efiok, B., Chepelinsky, A.B. and Egwuagu, C.E. Interferon Regulatory Transcription Factors (IRFs) are Constitutively Expressed and Spatially Regulated in the Mouse Lens. (Developmental Biology 210: 44-55, 1999).PubMed

Li, W., Nagineni, C.N., Ohtaka-Marayuma, C., Efiok, B., Chepelinsky, A.B. and Egwuagu, C.E. Interferon Consensus Sequence Binding Protein (ICSBP) is Constitutively Expressed and Differentially Regulated in the Ocular Lens. (J. Biol. Chem. 274:9686-9691, 1999).PubMed

Egwuagu, C.E., Sztein, J., Mahdi, R.M., Li, W., Chan, C.C., Smith, J.A. and Chepelinsky, A.B. Constitutive Expression of IFN-g in the Eye Exacerbates Anterior Uveitis and Induces Retinal Degenerative Changes in Transgenic Rats. (Clinical Immunology 91:196-205, 1999). PubMed

Li, W., Nagineni, C.N., Hooks, J.J., Chepelinsky, A.B. and Egwuagu, C.E. Intereferon-? Signaling in Human Retinal Pigment Epithelial Cells is Mediated by STAT1, ICSBP and IRF-1 Transcription Factors. (Invest. Ophthalmol. Vis. Sci. 40:976-982, 1999). PubMed

Egwuagu, C.E., Sztein, J., Mahdi, R.M., Li, W., Chan, C.C., Smith, J.A., Charukamnoetkanok, P. and Chepelinsky, A.B. Interferon-? (IFN?) Increases the Severity and Accelerates the Onset of Experimental Autoimmune Uveitis in Transgenic Rats. (J. Immunol. 162: 510-517, 1999). PubMed

Ebong S, Yu CR, Carper DA, Chepelinsky AB, Egwuagu CE. Activation of STAT signaling pathways and induction of suppressors of cytokine signaling (SOCS) proteins in mammalian lens by growth factors. (Invest Ophthalmol Vis Sci. 45:872-8, 2004). PubMed

Uveitis

Egwuagu, C.E., Charukamnoetkanok, P. and Gery, I. Thymic Expression of Autoantigens Correlates with Resistance to Autoimmune Disease. (J. Immunol. (Cutting Edge Paper) 159: 3109-3112, 1997). PubMed

Gery I and Egwuagu CE. Central tolerance mechanisms in control of susceptibility to autoimmune uveitic disease. (Intern. Rev. Immunol., 21: 89-100, 2002).PubMed

Egwuagu CE and Smith JA. Uveitis. (Emerging Therapeutic Targets, 4(6): 715-733, 2000).

Takase H, Yu CR, Mahdi RM, Douek DC, Dirusso GB, Midgley FM, Dogra R, Allende G, Rosenkranz E, Pugliese A, Egwuagu CE, Gery I. Thymic expression of peripheral tissue antigens in humans: a remarkable variability among individuals. (Int Immunol. 17:1131-40, 2005). PubMed

Egwuagu CE, Yu CR, Li Z, Nussenblatt RB. SOCS5 mRNA Levels in Peripheral Blood Mononuclear Cells (PMBC): A Potential Bio-Marker for Monitoring Response of Uveitis Patients to Daclizumab Therapy. (J. Autoimmunity 24:39-46, 2005). PubMed

Takase H, Yu CR, Liu X, Fujimoto C, Gery I, Egwuagu CE. Induction of Suppressors of Cytokine Signaling (SOCS) in the Retina during Experimental Autoimmune Uveitis (EAU): Potential Neuroprotective Role of SOCS Proteins (J. Neuroimmunology 168:118-127, 2005). PubMed

 

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