Our research interests concern development and function of γδ T cells, a class of immune cells with various roles in microbial immunity, regulation of inflammation, tumor surveillance and others. Unlike conventional αβ T cells, γδ T cells preferentially reside in epithelial tissues covering the surface of a body, where they function in the first line of defense. Using transgenic and knockout mouse models as experimental approaches, we try to uncover molecular mechanisms underlying development of tissue specific γδ T cells and define their functional mechanism in infection and inflammation.

Molecular mechanism of skin γδ T cell development
Murine skin γδ T cells are the most representative of tissue specific γδ T cells. They reside in epidermal layer of the skin and are involved in preventing cutaneous tumorigenesis, controlling skin inflammation, wound healing and others. All the skin γδ T cells express identical γδ T cell receptors (TCR) composed of canonical Vγ3+ TCRγ and Vδ1+ TCRδ chain and originate from the fetal thymus. Recently, we discovered that positive selection of the Vγ3+/Vδ1+ γδ T cells in the fetal thymus results in a coordinate switch in expression of a set of chemokine and cytokine receptors, which in turn direct migration and expansion of the positively selected γδ T cells in the skin (Figure 1). This finding establishes that central thymic selection of γδ T cells play an important role in their peripheral tissue distribution, a novel advance in understanding development of tissue-specific T cells. The fFuture research will focus on molecular events involved in the TCR-mediated positive selection, regulation of the chemokine receptor expression and its roles in skin γδ T cell development.

γδ T cells in regulation of local inflammatory responses
Recently, we found that mice deficient in certain subsets of γδ T cells spontaneously develop an inflammatory eye disease with high penetrance on a certain genetic background. Preliminary studies revealed that the eye problem is a form of allergic conjunctivitis (inflammation of conjunctiva, the mucosal tissue of eyelids), a kind of disease affecting millions of people in US. We will use this animal model to study functional mechanisms of γδ T cells in controlling local tissue inflammation, and elucidate etiology and polymorphic genetic links of the disease.

Xiong N, Kang C and Raulet DH. Positive selection of dendritic epidermal γδ T cell precursors in the fetal thymus determines expression of skin-homing receptors. Immunity 21(1): 121-131 (2004)

Xiong N, Baker JE, Kang C and Raulet DH. The genomic arrangement of T cell receptor variable genes is a determinant of the developmental rearrangement pattern. Proceedings of the National Academy of Science: 101(1): 260–265 (2004)

Xiong N, Kang C and Raulet DH. Redundant and unique roles of two enhancer elements in the TCRγ locus in gene regulation and γδ T cell development. Immunity 16(3): 453-463 (2002)