About My Research
Center/Research Area Affiliations
Biography
At Schepens Eye Research Institute of Mass. Eye and Ear, Dr. Chauhan’s research interests focus on immunomodulation and regenerative medicine for ocular surface injury and inflammatory disorders. His work has led to many important novel findings, including loss of function of regulatory T cells (Tregs) in corneal transplantation and the involvement of highly pathogenic Th17 cells in the immunopathogenesis of dry eye disease.
More recently, Dr. Chauhan has focused on using immunomodulatory and regenerative functions of Mesenchymal Stem Cells (MSCs) to treat ocular surface disorders. His research has recently demonstrated that MSCs have the capacity to restore corneal transparency by secreting high levels of hepatocyte growth factor. Dr. Chauhan is studying the function of immunoregulatory cells, including MSCs, Tregs, and myeloid suppressor cells, with the ultimate goal of using their therapeutic potential in ocular inflammation.
Dr. Chauhan is also Affiliate Faculty at Harvard Stem Cell Institute.
- Myeloid-derived suppressor cells promote allograft survival by suppressing regulatory T cell dysfunction in high-risk corneal transplantation. Am J Transplant. 2024 Mar 19.
- Effector T Cells Promote Fibrosis in Corneal Transplantation Failure. Invest Ophthalmol Vis Sci. 2024 Jan 02; 65(1):40.
- Interleukin-11 Suppresses Ocular Surface Inflammation and Accelerates Wound Healing. Invest Ophthalmol Vis Sci. 2023 11 01; 64(14):1.
- Mesenchymal Stromal Cells Suppress T-Cell-Mediated Delayed-Type Hypersensitivity via ALCAM-CD6 Interaction. Stem Cells Transl Med. 2023 04 17; 12(4):221-233.
- Increased activity of lacrimal gland mast cells are associated with corneal epitheliopathy in aged mice. NPJ Aging. 2023 Feb 27; 9(1):2.
- IL-36? Augments Ocular Angiogenesis by Promoting the Vascular Endothelial Growth Factor-Vascular Endothelial Growth Factor Receptor Axis. Am J Pathol. 2023 11; 193(11):1740-1749.
- Conventional type I migratory CD103+ dendritic cells are required for corneal allograft survival. Mucosal Immunol. 2023 Oct; 16(5):711-726.
- Amplified Natural Killer Cell Activity and Attenuated Regulatory T-cell Function Are Determinants for Corneal Alloimmunity in Very Young Mice. Transplantation. 2023 06 01; 107(6):1302-1310.
- Non-immune and immune functions of interleukin-36? suppress epithelial repair at the ocular surface. FASEB J. 2022 08; 36(8).
- Role of inflammatory cells in pathophysiology and management of diabetic retinopathy. Surv Ophthalmol. 2022 Nov-Dec; 67(6):1563-1573.
- A new non-human primate model of desiccating stress-induced dry eye disease. Sci Rep. 2022 05 13; 12(1):7957.
- Autoreactive memory Th17 cells are principally derived from T-bet+ROR?t+ Th17/1 effectors. J Autoimmun. 2022 05; 129:102816.
- Mesenchymal stem cells augment regulatory T cell function via CD80-mediated interactions and promote allograft survival. Am J Transplant. 2022 06; 22(6):1564-1577.
- Suppression of lipopolysaccharide-induced corneal opacity by hepatocyte growth factor. Sci Rep. 2022 01 11; 12(1):494.
- Ocular surface mast cells promote inflammatory lymphangiogenesis. Microvasc Res. 2022 05; 141:104320.
- The Neuropeptide Alpha-Melanocyte-Stimulating Hormone Is Critical for Corneal Endothelial Cell Protection and Graft Survival after Transplantation. Am J Pathol. 2022 02; 192(2):270-280.
- Spatial Distribution of Mast Cells Regulates Asymmetrical Angiogenesis at the Ocular Surface. Am J Pathol. 2021 06; 191(6):1108-1117.
- Pigment Epithelium-Derived Factor Enhances the Suppressive Phenotype of Regulatory T Cells in a Murine Model of Dry Eye Disease. Am J Pathol. 2021 04; 191(4):720-729.
- Growth factor-eluting hydrogels for management of corneal defects. Mater Sci Eng C Mater Biol Appl. 2021 Jan; 120:111790.
- Characterization of Clinical and Immune Responses in an Experimental Chronic Autoimmune Uveitis Model. Am J Pathol. 2021 03; 191(3):425-437.
- Activation of ocular surface mast cells promotes corneal neovascularization. Ocul Surf. 2020 10; 18(4):857-864.
- Steroid-eluting contact lenses for corneal and intraocular inflammation. Acta Biomater. 2020 10 15; 116:149-161.
- Epithelium-derived IL-33 activates mast cells to initiate neutrophil recruitment following corneal injury. Ocul Surf. 2020 10; 18(4):633-640.
- Restoration of Regulatory T-Cell Function in Dry Eye Disease by Antagonizing Substance P/Neurokinin-1 Receptor. Am J Pathol. 2020 09; 190(9):1859-1866.
- Pigment Epithelium-derived Factor secreted by corneal epithelial cells regulates dendritic cell maturation in dry eye disease. Ocul Surf. 2020 07; 18(3):460-469.
- The functions of IL-23 and IL-2 on driving autoimmune effector T-helper 17 cells into the memory pool in dry eye disease. Mucosal Immunol. 2021 01; 14(1):177-186.
- Aged Mice Exhibit Severe Exacerbations of Dry Eye Disease with an Amplified Memory Th17 Cell Response. Am J Pathol. 2020 07; 190(7):1474-1482.
- Neutrophil L-Plastin Controls Ocular Paucibacteriality and Susceptibility to Keratitis. Front Immunol. 2020; 11:547.
- Regulatory T cells promote corneal endothelial cell survival following transplantation via interleukin-10. Am J Transplant. 2020 02; 20(2):389-398.
- Corrigendum to TFOS DEWS II pathophysiology report [Ocul. Surf. 15 (3) (2017) 438-510]. Ocul Surf. 2019 Oct; 17(4):842.
- Therapeutic efficacy of different routes of mesenchymal stem cell administration in corneal injury. Ocul Surf. 2019 10; 17(4):729-736.
- The purinergic receptor antagonist oxidized adenosine triphosphate suppresses immune-mediated corneal allograft rejection. Sci Rep. 2019 06 13; 9(1):8617.
- Mesenchymal Stromal Cells Modulate Corneal Alloimmunity via Secretion of Hepatocyte Growth Factor. Stem Cells Transl Med. 2019 10; 8(10):1030-1040.
- The therapeutic application of mesenchymal stem cells at the ocular surface. Ocul Surf. 2019 04; 17(2):198-207.
- Local Delivery of Regulatory T Cells Promotes Corneal Allograft Survival. Transplantation. 2019 01; 103(1):182-190.
- Mast cells contribute to the induction of ocular mucosal alloimmunity. Am J Transplant. 2019 03; 19(3):662-673.
- The immunoregulatory role of corneal epithelium-derived thrombospondin-1 in dry eye disease. Ocul Surf. 2018 10; 16(4):470-477.
- Mast Cells Initiate the Recruitment of Neutrophils Following Ocular Surface Injury. Invest Ophthalmol Vis Sci. 2018 04 01; 59(5):1732-1740.
- Mesenchymal Stromal Cells Inhibit Neutrophil Effector Functions in a Murine Model of Ocular Inflammation. Invest Ophthalmol Vis Sci. 2018 03 01; 59(3):1191-1198.
- Interleukin-6 neutralization prolongs corneal allograft survival. Curr Trends Immunol. 2018; 19:105-113.
- When Clarity Is Crucial: Regulating Ocular Surface Immunity. Trends Immunol. 2018 04; 39(4):288-301.
- TFOS DEWS II Report Executive Summary. Ocul Surf. 2017 10; 15(4):802-812.
- TFOS DEWS II pathophysiology report. Ocul Surf. 2017 07; 15(3):438-510.
- IFN-?-Expressing Th17 Cells Are Required for Development of Severe Ocular Surface Autoimmunity. J Immunol. 2017 08 01; 199(3):1163-1169.
- Hepatocyte Growth Factor Suppresses Inflammation and Promotes Epithelium Repair in Corneal Injury. Mol Ther. 2017 08 02; 25(8):1881-1888.
- Effector and Regulatory T Cell Trafficking in Corneal Allograft Rejection. Mediators Inflamm. 2017; 2017:8670280.
- Treatment of donor corneal tissue with immunomodulatory cytokines: a novel strategy to promote graft survival in high-risk corneal transplantation. Sci Rep. 2017 04 20; 7(1):971.
- Proangiogenic Function of T Cells in Corneal Transplantation. Transplantation. 2017 04; 101(4):778-785.
- Mesenchymal Stem Cells Modulate Differentiation of Myeloid Progenitor Cells During Inflammation. Stem Cells. 2017 06; 35(6):1532-1541.
- T Cell-Derived Granulocyte-Macrophage Colony-Stimulating Factor Contributes to Dry Eye Disease Pathogenesis by Promoting CD11b+ Myeloid Cell Maturation and Migration. Invest Ophthalmol Vis Sci. 2017 02 01; 58(2):1330-1336.
- Lacrimal gland-derived IL-22 regulates IL-17-mediated ocular mucosal inflammation. Mucosal Immunol. 2017 09; 10(5):1202-1210.
- Interleukin-7 and -15 maintain pathogenic memory Th17 cells in autoimmunity. J Autoimmun. 2017 02; 77:96-103.
- Restoration of Corneal Transparency by Mesenchymal Stem Cells. Stem Cell Reports. 2016 10 11; 7(4):583-590.
- IL-17 Augments B Cell Activation in Ocular Surface Autoimmunity. J Immunol. 2016 11 01; 197(9):3464-3470.
- Ageing and ocular surface immunity. Br J Ophthalmol. 2017 Jan; 101(1):1-5.
- Alloimmunity and Tolerance in Corneal Transplantation. J Immunol. 2016 05 15; 196(10):3983-91.
- E-Selectin Mediates Immune Cell Trafficking in Corneal Transplantation. Transplantation. 2016 Apr; 100(4):772-80.
- In Vivo Expansion of Regulatory T Cells by Low-Dose Interleukin-2 Treatment Increases Allograft Survival in Corneal Transplantation. Transplantation. 2016 Mar; 100(3):525-32.
- Graft Site Microenvironment Determines Dendritic Cell Trafficking Through the CCR7-CCL19/21 Axis. Invest Ophthalmol Vis Sci. 2016 Mar; 57(3):1457-67.
- PTK7+ Mononuclear Cells Express VEGFR2 and Contribute to Vascular Stabilization by Upregulating Angiopoietin-1. Arterioscler Thromb Vasc Biol. 2015 Jul; 35(7):1606-15.
- VEGF-trap aflibercept significantly improves long-term graft survival in high-risk corneal transplantation. Transplantation. 2015 Apr; 99(4):678-86.
- Science and Art of Cell-Based Ocular Surface Regeneration. Int Rev Cell Mol Biol. 2015; 319:45-106.
- Quantification of allospecific and nonspecific corneal endothelial cell damage after corneal transplantation. Eye (Lond). 2015 Jan; 29(1):136-44.
- Mesenchymal stem cells home to inflamed ocular surface and suppress allosensitization in corneal transplantation. Invest Ophthalmol Vis Sci. 2014 Sep 16; 55(10):6631-8.
- The resolvin D1 analogue controls maturation of dendritic cells and suppresses alloimmunity in corneal transplantation. Invest Ophthalmol Vis Sci. 2014 Aug 21; 55(9):5944-51.
- CCR7 is critical for the induction and maintenance of Th17 immunity in dry eye disease. Invest Ophthalmol Vis Sci. 2014 Aug 19; 55(9):5871-7.
- Soluble vascular endothelial growth factor receptor-3 suppresses allosensitization and promotes corneal allograft survival. Graefes Arch Clin Exp Ophthalmol. 2014 Nov; 252(11):1755-62.
- A novel pro-angiogenic function for interferon-?-secreting natural killer cells. Invest Ophthalmol Vis Sci. 2014 May 02; 55(5):2885-92.
- Effects of topical Janus kinase inhibition on ocular surface inflammation and immunity. Cornea. 2014 Feb; 33(2):177-83.
- Corneal Lymphatics: Role in Ocular Inflammation as Inducer and Responder of Adaptive Immunity. J Clin Cell Immunol. 2014; 5.
- Expression of the chemokine decoy receptor D6 mediates dendritic cell function and promotes corneal allograft rejection. Mol Vis. 2013; 19:2517-25.
- CCL-21 conditioned regulatory T cells induce allotolerance through enhanced homing to lymphoid tissue. J Immunol. 2014 Jan 15; 192(2):817-23.
- The CCR6/CCL20 axis mediates Th17 cell migration to the ocular surface in dry eye disease. Invest Ophthalmol Vis Sci. 2013 Jun 12; 54(6):4081-91.
- Chronic dry eye disease is principally mediated by effector memory Th17 cells. Mucosal Immunol. 2014 Jan; 7(1):38-45.
- Effect of desiccating environmental stress versus systemic muscarinic AChR blockade on dry eye immunopathogenesis. Invest Ophthalmol Vis Sci. 2013 Apr 03; 54(4):2457-64.
- Nerves and neovessels inhibit each other in the cornea. Invest Ophthalmol Vis Sci. 2013 Jan 28; 54(1):813-20.
- Expression of toll-like receptor 4 contributes to corneal inflammation in experimental dry eye disease. Invest Ophthalmol Vis Sci. 2012 Aug 17; 53(9):5632-40.
- Change in prostaglandin expression levels and synthesizing activities in dry eye disease. Ophthalmology. 2012 Nov; 119(11):2211-9.
- b-FGF induces corneal blood and lymphatic vessel growth in a spatially distinct pattern. Cornea. 2012 Jul; 31(7):804-9.
- Kinetics and function of mesenchymal stem cells in corneal injury. Invest Ophthalmol Vis Sci. 2012 Jun 14; 53(7):3638-44.
- PDE4 inhibition suppresses IL-17-associated immunity in dry eye disease. Invest Ophthalmol Vis Sci. 2012 Jun 14; 53(7):3584-91.
- Efficacy of topical blockade of interleukin-1 in experimental dry eye disease. Am J Ophthalmol. 2012 Jul; 154(1):63-71.
- Vascular endothelial growth factor-C promotes alloimmunity by amplifying antigen-presenting cell maturation and lymphangiogenesis. Invest Ophthalmol Vis Sci. 2012 Mar; 53(3):1244-50.
- Ocular surface immunity: homeostatic mechanisms and their disruption in dry eye disease. Prog Retin Eye Res. 2012 May; 31(3):271-85.
- Dependence of corneal stem/progenitor cells on ocular surface innervation. Invest Ophthalmol Vis Sci. 2012 Feb 21; 53(2):867-72.
- Donor-derived, tolerogenic dendritic cells suppress immune rejection in the indirect allosensitization-dominant setting of corneal transplantation. J Leukoc Biol. 2012 Apr; 91(4):621-7.
- Dry eye disease: an immune-mediated ocular surface disorder. Arch Ophthalmol. 2012 Jan; 130(1):90-100.
- Therapeutic efficacy of topical epigallocatechin gallate in murine dry eye. Cornea. 2011 Dec; 30(12):1465-72.
- Blockade of prolymphangiogenic vascular endothelial growth factor C in dry eye disease. Arch Ophthalmol. 2012 Jan; 130(1):84-9.
- A novel pro-lymphangiogenic function for Th17/IL-17. Blood. 2011 Oct 27; 118(17):4630-4.
- Characterization of Langerin-expressing dendritic cell subsets in the normal cornea. Invest Ophthalmol Vis Sci. 2011 Jun 28; 52(7):4598-604.
- Effect of topical azithromycin on corneal innate immune responses. Invest Ophthalmol Vis Sci. 2011 Apr 19; 52(5):2525-31.
- A novel mouse model for neurotrophic keratopathy: trigeminal nerve stereotactic electrolysis through the brain. Invest Ophthalmol Vis Sci. 2011 Apr; 52(5):2532-9.
- Flt-1 regulates vascular endothelial cell migration via a protein tyrosine kinase-7-dependent pathway. Blood. 2011 May 26; 117(21):5762-71.
- A novel function for programmed death ligand-1 regulation of angiogenesis. Am J Pathol. 2011 04; 178(4):1922-9.
- Interferon-?-secreting NK cells promote induction of dry eye disease. J Leukoc Biol. 2011 Jun; 89(6):965-72.
- Thrombospondin-1 derived from APCs regulates their capacity for allosensitization. J Immunol. 2010 Oct 15; 185(8):4691-7.
- Evidence of corneal lymphangiogenesis in dry eye disease: a potential link to adaptive immunity? Arch Ophthalmol. 2010 Jul; 128(7):819-24.
- Effects of topical and subconjunctival bevacizumab in high-risk corneal transplant survival. Invest Ophthalmol Vis Sci. 2010 May; 51(5):2411-7.
- Contribution of macrophages to angiogenesis induced by vascular endothelial growth factor receptor-3-specific ligands. Am J Pathol. 2009 Nov; 175(5):1984-92.
- Role of CCR7 in facilitating direct allosensitization and regulatory T-cell function in high-risk corneal transplantation. Invest Ophthalmol Vis Sci. 2010 Feb; 51(2):816-21.
- Amelioration of murine dry eye disease by topical antagonist to chemokine receptor 2. Arch Ophthalmol. 2009 Jul; 127(7):882-7.
- Role of Th17 cells in the immunopathogenesis of dry eye disease. Mucosal Immunol. 2009 Jul; 2(4):375-6.
- Anti-angiogenesis effect of the novel anti-inflammatory and pro-resolving lipid mediators. Invest Ophthalmol Vis Sci. 2009 Oct; 50(10):4743-52.
- Characterization of effector T cells in dry eye disease. Invest Ophthalmol Vis Sci. 2009 Aug; 50(8):3802-7.
- 'Chimeric' grafts assembled from multiple allodisparate donors enjoy enhanced transplant survival. Am J Transplant. 2009 Mar; 9(3):473-82.
- Autoimmunity in dry eye is due to resistance of Th17 to Treg suppression. J Immunol. 2009 Feb 01; 182(3):1247-52.
- Depletion of passenger leukocytes from corneal grafts: an effective means of promoting transplant survival? Invest Ophthalmol Vis Sci. 2009 Jul; 50(7):3137-44.
- Levels of Foxp3 in regulatory T cells reflect their functional status in transplantation. J Immunol. 2009 Jan 01; 182(1):148-53.
- The role of ACAID and CD4+CD25+FOXP3+ regulatory T cells on CTL function against MHC alloantigens. Mol Vis. 2008; 14:2435-42.
- Regulation of blood vessel versus lymphatic vessel growth in the cornea. Invest Ophthalmol Vis Sci. 2009 Apr; 50(4):1613-8.
- Reactivity of gamma/delta T cells to human 60-kd heat-shock protein and their cytotoxicity to aortic endothelial cells in Takayasu arteritis. Arthritis Rheum. 2007 Aug; 56(8):2798-802.
- Antigenic targets and pathogenicity of anti-aortic endothelial cell antibodies in Takayasu arteritis. Arthritis Rheum. 2006 Jul; 54(7):2326-33.
- T-cell receptor repertoire of circulating gamma delta T-cells in Takayasu's arteritis. Clin Immunol. 2006 Feb-Mar; 118(2-3):243-9.
- Vaccines for control of Salmonellosis. J Immunol and Immunopathol. 2005; 7(1):1-7.
- Cellular and humoral immune responses to mycobacterial heat shock protein-65 and its human homologue in Takayasu's arteritis. Clin Exp Immunol. 2004 Dec; 138(3):547-53.
- Cytokine mRNA repertoire of peripheral blood mononuclear cells in Takayasu's arteritis. Clin Exp Immunol. 2004 Nov; 138(2):369-74.
- Comparative in vitro elution study of cefazolin antibiotic impregnated poly methyl methacrylate and plaster of paris beads. Indian Journal of Veterinary Surgery. 2003; 24(1):47-48.
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Immunomodulatory and Regenerative Functions of Mesenchymal Stem Cells in Ocular Injuries and Inflammation
The goal of this project is to identify and use the immunomodulatory and regenerative functions of mesenchymal stem cells (MSC) to treat ocular surface disorders. Since their discovery, MSCs have held tremendous promise for tissue regeneration, primarily due to their differentiation capacity. However, this represents only a portion of the vast potentials of MSCs in re-establishing tissue homeostasis, including their capacity to promote immune quiescence.
Little is known how MSCs modulate the host immune response. Although MSCs have been shown to suppress pathogenic immune cells, the specific molecular mechanisms by which MSCs directly promote the function of regulatory immune cells remain much less understood.
Dr. Chauhan is exploring the molecular mechanisms by which MSCs promote function of critical regulatory immune cells. In the setting of ocular inflammation and immunity, he is investigating how MSCs (1) promote generation of myeloid suppressor cells and (2) enhance the function of regulatory T cells.
His results from animal models of corneal injury (IOVS 2012, Stem Cells 2017) and transplantation (IOVS 2014) suggest that the immunomodulatory function of MSCs could effectively be used therapeutically. His is also evaluating the capacity and mechanisms of MSCs in restoring corneal transparency. Ocular injuries involving the cornea undergo a wound healing process that often results in scar formation and loss of corneal transparency. Dr. Chauhan has reported that MSCs are capable of restoring corneal transparency. Specifically, he has shown that (1) MSCs secrete high levels of hepatocyte growth factor (HGF), which inhibits the generation of opacity-inducing myofibroblasts and (2) that HGF alone can restore corneal transparency in an in vivo model of corneal stromal injury, suggesting a novel HGF-based therapeutic approach that could potentially eliminate the need for cell-based and conventional therapies (Stem Cell Reports 2016, Molecular Therapy 2017).
Dr. Chauhan believes that MSC-based treatments (cell-based or identified factors) could be a significant improvement over the current use of non-specific anti-inflammatory and immunosuppressive drugs, which are fraught with serious side effects.
Regulation of Innate Immune Responses in Ocular Injury
Eye injuries due to trauma, infection, and burns are common causes of ocular inflammatory disorders and blindness worldwide. Following injury, innate immune responses—primarily through recruitment of activated neutrophils to the eye—lead to deleterious inflammatory tissue damage and fibrosis. As neutrophils advance from the vasculature to the site of injury, they go through progressive stages of activation and release effector molecules, including tissue matrix-destructing enzymes myeloperoxidase (MPO) and N-elastase (ELAN).
Current treatments, such as steroids, not only suppress the protective immune response non-specifically, but are also associated with serious side effects, including infection, cataract, and glaucoma. Thus, there is a pressing need for new therapeutic strategies that can regulate innate inflammation by selectively inhibiting pathogenic neutrophil effector function.
Dr. Chauhan’s pilot studies indicate that during ocular inflammation, infiltrating neutrophils interact with non-hematopoietic tissue-resident stromal cells. These eye-resident stromal cells effectively regulate neutrophil effector functions, including the release of tissue-destructing MPO and ELAN. In this project, using a standard mouse model of ocular injury and a series of novel experiments, he is delineating critical mechanisms by which stromal cells regulate neutrophil effector function and promote reestablishment of immune quiescence in ocular inflammation.
Dynamics of Treg and Th17 Cells in Ocular Immunity
This project aims to determine the role of regulatory T cells (Tregs) and pathogenic Th17 cells, and their secreted cytokines in the induction of antigen-specific immunity and tolerance—both in corneal transplantation and autoimmune dry eye disease. His work has led to many important novel findings. He has reported the involvement of highly pathogenic and autoreactive Th17 cells in the immunopathogenesis of dry eye disease. Using a murine model of dry eye disease, he clearly demonstrated that in vivo inhibition of Th17/IL17 pathway leads to amelioration of both the induction and progression of the disease (J Immunol, 2009; Blood 2011). He also established that levels of Foxp3 in Tregs reflect their functional status in transplantation, and reported an association between Treg function and corneal allograft survival (J Immunol 2009; J Immunol 2014). He is now developing strategies for clinical translation of our novel research findings, particularly a Treg cell-based therapy to promote allograft survival and a Th17/IL17-antagonist-based immunotherapy for dry eye disease.
Current Members of Dr. Sunil Chauhan’s Laboratory
Administrative Coordinator
- Linda Benson
Senior Research Associate
- Sharad Mittal, PhD
Postdoctoral Fellows
- Afsaneh Amouzegar, MD
- Mingshun Li, MD
- Sayed Basiony, MD
- Sachin Shukla, PhD
Graduate Student
- Disha Singhania (U Cambridge)
Alumni
To date, more than six trainees have worked in Dr. Chauhan’s laboratory.