Immunology Faculty Member - Reza Dana, MD

Reza Dana, MD

CH Dohlman Professor and Senior Scientist

The Schepens Eye Research Institute
20 Staniford Street

Boston, MA 02114
Tel: 617-912-7401
Email: Reza_Dana@meei.harvard.edu
Visit my lab page here.



Assistant: Linda Benson, Email: linda_benson@meei.harvard.edu

Research Interests
Our lab’s major focus is on the mechanisms by which both immune and non-hematopoietic (tissue resident) cells maintain immune quiescence. Our work has been instrumental in determining the cytokine ligands and receptors (including decoy non-signaling receptors) that maintain the eye’s immune and angiogenic privilege. Since these regulatory functions are susceptible to failure in states of high inflammation, we are also interested in (i) determining the mechanisms that lead to abrogation of the normal regulatory functions of immune cells and (ii) cytokine targeting strategies that can counter-balance these pathogenic mechanisms for restoring immune homeostasis. Our work has uncovered numerous mechanisms that regulate antigen-presenting/dendritic cell maturation and mobilization in the eye and lymphoid tissues, interactions between immune cells, including effector and regulatory T cells (Treg), with the ocular surface epithelium and vascular endothelium, and more recently Treg plasticity and regulatory breakdown in chronic inflammation. Our more recent program is focused on the effect of aging on the Treg-memory T cell balance.

Specific Projects
1. Regulatory T cells (Treg)- Our aim is to define the plasticity and functional range of Tregs in ocular transplantation and autoimmunity. We have identified multiple phenotypes of Tregs and defined the microenvironmental contexts in which Treg lose their immunoregulatory function. We have (i) identified Treg susceptibility to Th17-associated cytokines as underpinning chronic ocular surface autoimmunity, (ii) identified Treg plasticity as a key factor in loss of allotolerance, and have (iii) defined novel strategies to enhance Treg homing to the immune synapse for induction of graft tolerance.
2. Corneal Transplantation- Our group has been at the forefront of corneal transplantation immunology research, evaluating the pathways (direct vs. indirect) of host T cell sensitization in hosts with various degrees of risk for rejection. Our work was the first to demonstrate that the graft site microenvironment (in any form of transplant) can have a profound effect on the host pathway of allosensitization.
3. Angiogenesis and Lymphangiogenesis- Our lab has deciphered the differential contributions of blood vs. lymphatic vessels to antigen-specific immunity, establishing how blood and lymphatic vessels amplify the ‘efferent’ (effector) and ‘afferent’ (inductive or sensitization) phases of antigen-specific immunity in the eye. We also were the first to publish on the cornea-specific expression of the membrane-bound VEGFR-3 decoy receptor, showing how its binding to relevant ligands, VEGF-C/D, can actively maintain the cornea free of both blood and lymphatic vessels.
4. Antigen-Presenting Cells (APC)- The dominant paradigm for many years in ocular immunology was that “corneal immune privilege” was due to the cornea being devoid of any functional APC. However, our lab demonstrated in a series of papers that the cornea is indeed populated by a heterogeneous population of bone marrow-derived cells that maintain a highly immature phenotype which renders them capable of antigen pickup but poor in sensitizing T cells. Subsequent studies showed how these APC alter their phenotype in response to different inflammatory insults and what mechanisms regulate their trafficking to the lymphoid compartment for priming antigen-specific T cell responses.
5. Ocular Surface Autoimmunity and Dry Eye Disease (DED)- Our work has focused on the role of T helper-17 (Th17) cells in dry eye pathogenesis. We have shown that in chronic disease, even without ongoing desiccating stress, there is generation of memory Th17s that are critical in maintaining chronic ocular surface epithelial damage. Ongoing research is focused on determining factors that maintain Th17 memory in DED and contribution of different Th17 effectors to the memory pool.



Last Update: 7/2/2018



Publications

Liu Y, Hamrah P, Zhang Q, Taylor AW, Dana R. Draining lymph nodes of corneal transplant hosts exhibit evidence for donor MHC class II-positive dendritic cells derived from MHC class II-negative grafts. J Exp Medicine 2002; 195: 259-68.

Huq S, Liu Y, Benichou G, Dana R. Relevance of the direct pathway of sensitization in corneal transplantation is dictated by the graft bed microenvironment.
J Immunol 2004: 173:4464-9.

Chen L, Hamrah L, Cursiefen C, Zhang Q, Pytowski B, Streilein JW, Dana R. Vascular Endothelial Growth Factor Receptor-3 (VEGFR-3) mediates induction of immunity to corneal transplants.
Nature Med 2004; 10: 813-815.

Cursiefen C, Chen L, Saint-Geniez M, Hamrah P, Jin Y, Rashid S, Pytowski B, Persaud K, Wu Y, Streilein JW, Dana R. Nonvascular VEGFR-3 expression by corneal epithelium maintains avascularity and vision.
Proc Nat Acad Sci USA 2006: 103:11405-10.

Shen L, Jin Y, Freeman GJ, Sharpe AH, Dana R. The function of donor versus recipient PD-L1 in corneal allograft survival.
J Immunology 2007; 179: 3672-9.

Chauhan SK, El Annan J, Ecoiffier T, Goyal S, Zhang Q, Saban DR, Dana R. Autoimmunity in dry eye is due to resistance of Th17 to Treg suppression.
J Immunology 2009; 182: 1247-52.

Chauhan SK, Jin Y, Goyal S, Lee HS, Fuchslugar T, Lee HK, and Dana R. A novel pro-lymphangiogenic function for Th17/IL17.
Blood. 2011; 118:4630-4.



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