Mechanisms of Salivary and Lacrimal Inflammation

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DESCRIPTION: The migration of autoreactive and effector lymphocytes from blood into salivary and lacrimal glands is a key event in the initiation and maintenance of glandular inflammation and damage in Sjogren?s syndrome. This migration involves a multi-step cascade with sequential lymphocyte/endothelial adhesion and activation events. The goals are to identify lymphocyte and endothelial adhesion molecules, chemokines, and chemokine receptors that are expressed in inflamed salivary and lacrimal glands, and to define the roles of these molecules in lymphocyte migration to these tissues. Non-obese diabetic (NOD) mice, a well-characterized model for human Sjogren?s syndrome, will be used for these studies. Specific Aim 1 will define the expression of adhesion molecules, chemokines, and chemokine receptors in inflamed salivary and lacrimal glands from NOD mice. The roles of these adhesion molecules and chemokines (and their receptors) in lymphocyte migration to inflamed glands will be assessed in functional studies in Specific Aim 2. Specific Aim 3 will determine if treatment of NOD mice with antibodies directed against adhesion molecules or chemokines defined in Aims 1 and 2 will prevent the development of salivary and lacrimal gland inflammation.