Insoo Kang, M.D.

Associate Professor of Medicine
Rheumatology

Research Activities

My laboratory investigates human T cell biology, focusing on immunosenescence and autoimmunity. Aging is associated with diminished immune responses against pathogens and malignancy. However, the underlying mechanisms for these findings are largely unknown. Recently, we investigated the effect of aging on the IL-7-mediated CD8 + T cell survival since IL-7 is critical for the generation and survival of memory CD8 + T cells. Cells expressing IL-7 receptor (R) alpha (a) high and low were identified in CD45RA+ effector memory (EM CD45RA+, CD45RA+ CCR 7+) CD8+ T cell subset. The elderly (age ≥ 65) had an increased frequency of EM CD45RA+ IL-7Ra low CD8+ T cells leading to decreased signaling and survival responses to IL-7 compared to the young (age ≤ 40). These EM CD45RA+ IL-7Ralow cells were largely antigen-experienced (CD27- CD28-), replicatively senescent (CD57+) and perforin high CD8+ T cells that had decreased IL-7Ra mRNA expression. These findings indicate that aging affects IL-7Ra expression by EM CD45RA+ CD8+ T cells, leading to impaired signaling and survival responses to IL-7.

Currently, we are investigating the mechanisms for how IL-7Ralow memory CD8+ T cells maintain low levels of IL-7Ra mRNA expression focusing on epigenetic regulation of genes. In addition, we are studying how IL-7Ralow memory CD8+ T cells are maintained despite impaired survival and proliferation in response to IL-7 and T cell receptor (TCR) triggering, respectively. We are also analyzing the effect of aging on regulatory T cells in humans. Lastly, our lab investigates alterations in T cell phenotype and function in patients with lupus in collaboration with Dr. Joe Craft. Recently, we reported that patients with lupus have defective control of latent Epstein- Barr virus (EBV) infection as evidence by increased EBV viral loads that stem from altered T cell immune responses to EBV. Our research will advance our understanding in the areas of immunosenescence and autoimmunity.

Selected Publications

• Kyung-A Hwang, H.R. Kim, S.H. Lee, S.W. Kang, and I. Kang. The effect of aging on CD4+ Foxp3+ T cells in humans. Manuscript submitted.
• Hang-Rae Kim*, K.A. Hwang* and I. Kang. Dual roles of IL-15 in maintaining IL-7R alpha low CCR7- memory CD8+ T cells in humans via recovering the PI3K/AKT pathway. J. Immunol. 179:6734-6740 *Equally contributed to this work.
• Hang-Rae Kim, K.A. Hwang and I. Kang. The role of DNA methylation in differentially regulating IL-7R alpha expression in human T cells. J. Immunol. 178:5473-9.
• Hang-Rae Kim, M.S. Hong, J.M. Dan and I. Kang. Altered IL-7R alpha expression with aging and the potential implications of IL-7 therapy on CD8+ T cell immune responses. Blood. 107:2855-2862, 2006.
• Insoo Kang, T. Quan, H. Nolasco, S.H. Park, M.S. Hong, G.J. Howe and J. Craft. Defective control of latent EBV infection in patients with systemic lupus erythematosus. J. Immunol. 172:1287-94, 2004.
• Insoo Kang, M.S. Hong, H. Nolasco, S.H. Park , J.M. Dan, J.Y. Choi and J. Craft. Age-associated change in the frequency of memory CD4+ T cells impairs long-term CD4+ T cell responses to influenza vaccine. J. Immunol. 173:673-681, 2004.
• Myung Sun Hong, J. M. Dan, J.Y. Choi and I. Kang. Age-associated changes in the frequency of naïve, memory and effector CD8+ T cells. Mech. Age. Dev. 125:615-618, 2004.

Lab Members

Associate Research Scientist
Won-Woo Lee, Ph.D.	(203) 785-3164
Research Associates
Amy Shelton	(203) 737-2247
Visiting Faculty
Seung-Hyun Lee, M.D. Ph.D.	(203) 785-3164
Jin-Soo Lee, M.D.	(203) 785-3164

Contact

Campus Address
300 Cedar Street
TAC S-541C

Mailing Address
Yale University School of Medicine
P.O. Box 208031
New Haven, CT 06520-8031

E-mail
insoo.kang@yale.edu

Office Phone
(203) 785-2453

Fax
(203) 785-7053