Insoo Kang, MD

Associate Professor of Medicine (Rheumatology); Course Director, Rheumatology Grand Rounds

Research Interests

Aging; Rheumatology; T-Lymphocytes; Autoimmunity

Research Organizations


Internal Medicine: Rheumatology

Skin Diseases Research Center, Yale

Stem Cell Center, Yale

Research Summary

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.

Specialized Terms: Human T cell biology; Immunosenescence; Autoimmunity

Extensive Research Description

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

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