Immunohistochemical study of tyrosine phosphorylation signaling in the involuted thymus

Thymic involution has been reported to be an important parameter of the degree and duration of child abuse. In the present study, we assessed the status of tyrosine phosphorylation signaling, which is known to play a key role in the physiological function of the thymus, in involuted thymuses of abused children through immunohistological studies performed with anti-phosphotyrosine antibodies. We found that tyrosine-phosphorylated proteins were present in high amounts in Hassall's corpuscles (HC) in the medulla of control thymuses. In involuted thymuses of abused children, expression of tyrosine-phosphorylated proteins was reduced with accompanying morphological changes of HC, such as reduction in size or calcification. These findings lead us to the suggestion that tyrosine phosphorylation signaling is reduced in involuted thymuses of abused children and that reduction of the signaling may be associated with morphological changes of HC as observed in involuted thymuses of abused children. In order to certify the suggestion, we investigated expression of tyrosine-phosphorylated proteins in involuted thymuses of stressed rats as well as in control thymuses. Immunohistochemistry revealed that tyrosine-phosphorylated proteins were expressed in control thymuses, more abundantly in the medulla, and reduced remarkably in involuted thymuses of stressed rats. Further, immunoblot analysis also showed that expression of phosphotyrosine-containing proteins was reduced in thymus extracts of involuted thymuses of stressed rats, thus supporting the suggestion. Our results also raise the possibility that components of tyrosine phosphorylation signaling could be a molecular marker for thymic involution.