Our Research Objectives

Regulation of lymphocyte homing in health and disease

The surveillance of the body for foreign antigens is a critical function of the immune system. Lymphocytes migrate from the blood into tissues and secondary lymphoid organs, and return to the blood via lymph vessels and the thoracic duct. Naïve T lymphocytes traffic through the T cell areas of secondary lymphoid organs in search of antigen presented by dendritic cells. Upon antigen recognition, specific T cells proliferate and, in the presence of polarizing cytokines, differentiate towards Th1 or Th2 lineages, which produce distinct patterns of cytokines and mediate different types of protective and pathological responses. While our knowledge of positive signals that regulate migration of lymphocytes to the LNs is large, little is known about the molecular mechanisms that negatively control or prevent the homing of cells to these sites. Our studies focus on the pathways that restrict homing of specific subsets of immune cells and thereby fine tune the immune response at specific lymphoid and peripheral sites.

We have previously characterized two pathways that inhibit B and T cell homing. The first one involves the secretion of low dose IFN-, and the second is regulated by the chemokine receptor, CCR2, and its ligand, CCL2. Both pathways attenuate lymphocyte chemotaxis towards lymph node chemokines. Impaired homing of lymphocytes to peripheral lymph nodes results in attenuated progression of inflammatory diseases like asthma and adjuvant-arthritis, IBD and EAE. Thus, low dose of IFN-γ and CCL2 can exert global suppressory effects on T cell trafficking and differentiation within peripheral lymph nodes and may be clinically beneficial as anti-inflammatory agents.

CCL2 plays an anti-inflammatory role an asthma in vivo model

Lung histology in mice that received CCL2 treatment. Histologic features of representative control (PBS), ova-primed (OVA) and ova-primed treated with low dose CCL2 (CCL2) animals are shown.