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Biomedical subjects

Matthew Erickson

Publications and source records attributed to Matthew Erickson.

4 recordsLinked to original sources

Cervical thymus in the mouse.

Although thymic ectopy has long been recognized in humans, the functional activity or potential immunological significance of this thymic tissue is unknown. In this study, we describe murine thymic ectopy, cervical thymic tissue that possesses the same general organization as the thoracic thymus, that is able to support T cell differentiation, and that can export T cells to the periphery. Unexpectedly, the pattern of autoantigen expression by ectopic thymic tissue differs from that of the thoracic thymus, raising the possibility that these two thymic environments may project different versions of self.

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Impaired skin blood flow response to environmental heating in chronic heart failure.

AIMS: We examined the thermoregulatory response to heat exposure in patients with chronic heart failure. METHODS AND RESULTS: Skin blood flow (SkBF) was measured in HF subjects and matched controls. Cutaneous vascular conductance (CVC) was calculated from laser-Doppler SkBF and blood pressure. To assess the nitric oxide contribution to thermoregulatory responses, subcutaneous microdialysis membranes were placed beneath the laser-Doppler probes to infuse N(G)-nitro-l-arginine methyl ester (l-NAME), or Ringer's solution. Core (T(C)) and skin temperatures (five sites, T(Sk)) were continuously recorded. Subjects were studied during normothermia then at 38 degrees C, 50%RH within a climate chamber. T(C) and T(Sk) did not differ between HF and controls during normothermia and heating induced similar increases in both groups. During heating, CVC rose in both groups, but significantly less so in HF (HF 43.9+/-7.8 vs. controls 58.0+/-7.5% CVC(max), P<0.05). l-NAME attenuated SkBF responses in the control (58.0+/-7.5 vs. 34.6+/-5.1% CVC(max), P<0.001) and HF subjects (43.9+/-7.8 vs. 27.0+/-2.2% CVC(max), P<0.005), with a larger effect evident in the controls (P<0.05). CONCLUSION: HF patients exhibit impaired thermoregulatory responses to heat exposure. Lower SkBF in HF, which defends blood pressure during heat exposure, also predisposes these subjects to heat intolerance.

Blood Flow Velocity↗

Nude thymic rudiment lacking functional foxn1 resembles respiratory epithelium.

The epithelial compartment of the thymus arises from endoderm of the 3rd pharyngeal pouch. As it moves from a cervical to a mediastinal position during development, this epithelium becomes populated by lymphoid progenitor cells from the blood and begins to support their differentiation along the T cell lineage. Productive differentiation of thymic epithelium is strictly dependent on the foxn1 transcription factor, as evidenced by the lack of functional thymic tissue in nude mice that carry a spontaneous loss-of-function mutation of foxn1. Evaluation of the thymic rudiment epithelium from nude mice revealed phenotypic properties and tissue organization that was strongly reminiscent of respiratory epithelium. These data suggest that foxn1 may be involved in directing lineage choices of multi-potential progenitor epithelial cells rather than simply affecting the terminal differentiation program of epithelial cells specified to a thymic fate.

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Regulation of thymic epithelium by keratinocyte growth factor.

Here we demonstrate that keratinocyte growth factor (KGF) and FGFR2IIIb signaling can affect development and function of thymic epithelium (TE) and that alphabeta-lineage thymocytes contribute to intrathymic levels of KGF. Thymocyte expression of KGF is developmentally regulated, being undetectable in CD3-4-8- thymocytes and expressed at highest levels by mature CD4 or CD8 thymocytes. Exposure of thymocyte-depleted fetal thymic lobes to KGF resulted in reduced thymic epithelial expression of class II major histocompatibility complex (MHC), invariant chain (Ii), and cathepsin L (CatL) molecules involved in thymocyte-positive selection and also stimulated expression of the cytokines interleukin 6 (IL-6) and thymic stromal-derived lymphopoietin (TSLP), while having little effect on IL-7 or stem cell factor expression. Within intact fetal thymic organ culture (FTOC), exogenous KGF impairs the generation of CD4 thymocytes. Two lines of evidence point to responsiveness of the medullary TE compartment to KGF and FGFR2IIIb signaling. First, the medullary compartment is expanded in intact FTOC exposed to KGF in vitro. Second, in the RAG-deficient thymus, where the thymocytes do not express detectable levels of KGF message, the hypoplastic medullary TE compartment can be expanded by administration of recombinant KGF in vivo. This expansion is accompanied by restoration of the normal profile of medullary TE-associated chemokine expression in the RAG2(-/-) thymus. Collectively, these findings point to a role for KGF and FGFR signaling in the development and function of thymic epithelium.

Animals↗