Project Summary The long lasting decrease of saliva secretion, also called dry mouth, is common in patients treated with radiotherapy for head and neck cancer. This side effect significantly impairs the quality of life of affected patients and is difficult to remedy. The applicant’s recent work revealed that macrophages abundant in salivary glands are sharply damaged by radiotherapy, and their recovery is required for restoring saliva secretion. The goals of this proposal are to determine the roles of local macrophages in the development, maintenance and regeneration of salivary glands, and how these cells respond to radiation and restore salivary function damaged by radiation. To achieve these goals, this project will trace the origin of local macrophages under conditions mentioned above, determine effects of removing these cells on salivary function, and pinpoint which molecules are responsible for the damage of these cells by radiation and for the recovery of salivary function damaged by radiation. Completion of this project will reveal vital roles of local macrophages and their products in the maintenance of saliva secretion, and form a basis for developing novel and feasible approaches to treating dry mouth caused by radiotherapy.