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Grant Abstract: Monocyte Regulation of Infant Immune Responses

Grant Number: 4R01AI100129-05
PI Name: Knight (et al Iwashima)
Project Title: Monocyte Regulation of Infant Immune Responses

Abstract: In this project, we will determine cellular and molecular changes in fetal and neonatal peripheral blood monocytes and T cells caused by supplementation of calcitriol , the active form of vitamin D. The goal of the main grant is to determine the functions of monocytes in the infant immune system whereby CD36hi CD14+ monocytes induce Foxp3+ regulatory T cells very efficiently. In the recent study using adult peripheral blood mononuclear cells (PBMCs), we identified two profound changes in T cells induced by calcitriol. One is reduction of a transcription factor Ahr and its downstream target BATF. The other is an increase of cytotoxic molecule TRAIL and acquisition of cytotoxic function. In this supplement, we will determine if calcitriol has the same effect on T cells and if supplementation of calcitriol in the culture changes differentiation of Foxp3+ Tregs from human umbilical cord blood or infant PBMCs. Successful completion of the study will provide unique and novel aspects of how calcitriol modulates the immune responses during the early child development. Since vitamin D is a commonly present nutrient and frequently used as the nutritional supplement, understanding of these molecular events can benefit promotion of health for many.

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