The goal of our project is to investigate the mechanisms of human lymphocyte responses in viral infection at the ocular surface and to develop new strategies to treat and prevent ocular viral infections.

The human ocular surface is rich in cells of mucosal immunity that comprise Conjunctiva-Associated Lymphoid Tissue (CALT). Amongst the cell populations, natural killer (NK) cells are lymphocytes of innate immunity and are important in the early response against viral pathogens and in inducing adaptive immunity. The epithelial cells of the conjunctiva and cornea are also important components of innate immunity.

Viral epidemic conjunctivitis caused by adenoviruses and enteroviruses are major medico-social problems especially in densely populated regions where millions of individuals suffer from ocular pain and visual disturbance. However, there are no prophylactic and therapeutic medicines for these diseases.

BIOGRAPHY

Nobuyo Yawata graduated from Yokohama City University Medical School in 1992. She is board-certified as an ophthalmologist in Japan, having trained with Professor Shigeaki Ohno, one of Japan’s top specialists in uveitis research. After she was awarded her Ph.D. degree in 2001, she conducted postdoctoral research on the diversity of human natural killer cell receptors in Stanford University School of Medicine, in Professor Peter Parham’s laboratory. She joined the SICS Infection and Immunity Program in August 2010.

Nobuyo Yawata is an adjunct research scientist in Singapore Eye Research Institute

MEMBERSHIP:

• Japanese Ophthalmological Society
• Japan Ophthalmologists Association
• Japanese Society for Immunology
• The Association for Research in Vision and Ophthalmology
• Singapore Eye Research Institute (Adjunct Research Scientist)

1. Characterizing the lymphocyte subsets at the human ocular surface
   Although rich in lymphocytes, details of the subsets at the human ocular surface await investigation. Our investigation aims to characterize the profiles and functions of ocular surface lymphocyte populations using high-dimensional flow cytometry and histology.
2. Investigating the immunomodulatory effects of ocular surface epithelial cells
   Ocular surface epithelial cells express various molecules used for viral entry and recognition. Epithelial cells also express arrays of chemokines and cytokines which modulate lymphocyte functions. Using both in vitro models and patient samples, we aim to identify how ocular surface epithelial cells respond to viral infection, and to analyse how ocular lymphocytes detect and respond to virally infected epithelial cells.
3. Identification of immune factors correlated with severity of viral conjunctivitis
   Viral conjunctivitis presents with various symptoms. Severe cases show chemosis, pseudomembranes, corneal epithelial disturbance, and subepithelial infiltration of lymphocytes which causes visual impairment for weeks to months. Our aim is to develop balanced immunotherapy that enables clearance of viral infection without causing excessive inflammation

Yawata M, Yawata N. NK cell KIR heterogeneity and evolution. Book chapter. Natural Killer Cells 2010;79-94. Elsevier publishing.

Sharma D, Bastard K, Guethlein LA, Norman PJ, Yawata N, Yawata M, Pando M, Thananchai H, Dong T, Rowland-Jones, S, Brodsky FM, Parham P. Dimorphic motifs in D0 and D1+D2 domains of KIR3DL1 combine to form receptors with high, moderate and no avidity for the complex of a peptide derived from human immunodeficiency virus and HLA-A*2402. Journal of Immunology 2009; 183:4569-4582.

Yawata M, *Yawata N, Draghi M, Partheniou F, Little AM, Parham P. MHC class I-specific inhibitory receptors and their ligands structure diverse human NK cell repertoires toward a balance of missing-self response. Blood 2008; 112:2369-2380.

Moesta AK, Norman PJ, Yawata M, Yawata N, Gleimer M, Parham P. Synergistic polymorphism at two positions distal to the ligand-binding site makes KIR2DL2 a stronger receptor for HLA-C than KIR2DL3. Journal of Immunology 2008; 180:3969-3979.

Yawata M, Yawata N, Parham P. Functional significance of KIR and HLA polymorphisms. Transplantation Now 2007; 11-22.

Thananchai H, Gillespie G, Martin M, Bashirova A, Yawata N, Yawata M, Easterbrook P, McVicar DW, Maenaka K, Parham P, Carrington M, Dong T, Rowland-Jones S. Allele-specific and peptide-dependent interactions between KIR3DL1 and HLA-A and -B. Journal of Immunology 2007; 178:33-37.

Yawata M, *Yawata N, Draghi M, Little AM, Partheniou F and Parham P. Roles for HLA and KIR polymorphisms in natural killer cell repertoire selection and modulation of effector function. Journal of Experimental Medicine 2006; 203:633-645.

Draghi M, Yawata N, Gleimer M, Yawata M, Valiante NM, Parham P. Single cell analysis of the human NK cell response to missing self and its inhibition by HLA class I. Blood 2005; 105:2028-2035.

Yawata M, Yawata N, Abi-Rached L, Parham P. Variation within the human Killer cell Immunoglobulin-like receptor (KIR) gene family. Critical Reviews in Immunology 2002; 22:463-482.

Matsumoto T, Yoshikawa M, Shigetou M, Enomoto Y, Nishi M, Yawata N. Cataract surgery in 2 cases of nanophthalmos: case reports. Atarashii-Ganka 2002; 4:517-520.

Yawata M, Yawata N, McQueen K, Cheng N, Guethlein L, Rajalingam R, Shilling H, Parham P. Predominance of group A KIR haplotypes in Japanese associated with diverse NK cell repertoires of KIR expression. Immunogenetics 2001; 54:543-550.

Yawata N, Ohno S. Acute retinal necrosis. Ganka 2000; 42:1567-1570.

Yawata N, Nakamura S, Kijima M, Ikai N, Kanai M, Sugita M, Ohno S. High incidence of glucose intolerance in Vogt-Koyanagi-Harada disease. British Journal of Ophthalmology 1999; 83: 39-42.

Yawata N, Kamata K. Exogenous intraocular inflammations. (in Japanese) Book chapter. Infectious and Immune-related ocular diseases 1997; 88-89, Medical View Sha Publishing.

Yawata N, Kamata K. Tumors. (in Japanese) Book chapter. Conjunctival Clinic 1997; 84-86, Igakushoin Publishing.

Kuma N, Kanai H, Hatano H, Ohno S. A case of bilateral multiple corneal opacity in Cri-du-chat syndrome. Atarashii-Ganka 1994; 11: 393-394.

TAN Kim Peng

Kevin John SELVA