Dr. Robert Tigelaar's major research focus continues to be the dendritic epidermal d T cells (DETC) populating the skin of all normal strains of mice. A number of longstanding collaborations between the Tigelaar lab and those of Michael Girardi (Dermatology) and Adrian Hayday (Guy’s Immunobiology [London]) include:
Adoptive transfer studies showed that Vg5+ DETC but not systemic Vg5- d cells were necessary and sufficient to down-regulate SpD. Finally, crosses of susceptible (NOD) and resistant (C57BL/6) d-/- mice which showed that susceptibility to SpD behaves as a recessive trait, have been recently analyzed by genome-wide, microsatellite mapping; these studies clearly indicate that several distinct genetic intervals contribute to the regulation of this cutaneous inflammatory response. Ongoing studies in this arena:
Specialized Terms: Immunobiology of gdT cells; Immune system-skin interactions; Immunopathogenesis of contact dermatitis, atopic dermatitis, and cutaneous T-cell lymphoma
Dr. Robert Tigelaar's major research focus continues to be the dendritic epidermal d T cells (DETC) populating the skin of all normal strains of mice. A number of longstanding collaborations between the Tigelaar lab and those of Michael Girardi (Dermatology) and Adrian Hayday (Guy’s Immunobiology [London]) include:
Adoptive transfer studies showed that Vg5+ DETC but not systemic Vg5- d cells were necessary and sufficient to down-regulate SpD. Finally, crosses of susceptible (NOD) and resistant (C57BL/6) d-/- mice which showed that susceptibility to SpD behaves as a recessive trait, have been recently analyzed by genome-wide, microsatellite mapping; these studies clearly indicate that several distinct genetic intervals contribute to the regulation of this cutaneous inflammatory response. Ongoing studies in this arena:
Recent studies of a spontaneous mutation arising in a substrain of FVB mice that results in a striking deficiency in the skin of the prototypic Vg5/Vd1+ DETCs seen in other normal mice strains led to further studies that proved that this heritable defect in a dominant gene resided in fetal thymic epithelial cells resulting in a failure of positive selection in the thymus (and subsequent migration to the skin) of the Vg5/Vd1+ fetal thymic precursors. (These results, published in Nature Immunology, present the first definitive proof that d cells resident in epithelial interfaces with the external environment, like conventional recirculating aß T cells, undergo positive selection in the thymus.) In a productive collaborative followup study between Drs. Tigelaar, Girardi and Hayday with Richard Lifton (Genetics) recently published in Nature Genetics, it was shown that this defect is caused by mutation in Skint1, a newly identified gene expressed in thymus and skin that encodes a protein with immunoglobulin-like and transmembrane domains. Skint1 is the prototypic member of a rapidly evolving family of at least 11 genes in mouse, with greatest similarity to the butyrophilin genes. These findings define a new family of proteins mediating key epithelial-immune interactions.
Dermatitis, Atopic; Dermatitis, Contact; Dermatology; Immune System; Skin; Lymphoma, T-Cell, Cutaneous