Lymphoid Tissue Inducer Cells in Intestinal Immunity

Howard Hughes Medical Institute, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA [email protected]

1 Introduction 60

2 Development of Organized GALT Structures 60

2.1 Functions of RORyt in Lymphoid Organogenesis and T Cell Development 61

2.2 Structure and Function of Organized GALT Structures 64

2.2.1 Peyer's Patches 65

2.2.2 Isolated Lymphoid Follicles 67

2.2.3 Cryptopatches 70

2.3 Cryptopatches as Organizing Centers for Localized Mucosal Responses . . 71

3 Dendritic Cells, a Double-Edged Sword 73

4 LTi Cells and Ectopic Lymphoid Follicles in Autoimmunity 77

5 Conclusions 77

References 78

Abstract During fetal development, lymphoid tissue inducer cells (LTis) seed the developing lymph node and Peyer's patch anlagen and initiate the formation of both types of lymphoid organs. In the adult, a similar population of cells, termed lymphoid tissue inducer-like cells (LTi-like cells), supports the formation of organized gut-associated lymphoid tissue (GALT) in the intestine, including both isolated lymphoid follicles (ILFs) and cryptopatches (CPs). Both LTi and LTi-like cells require expression of the transcription factor RORyt for their differentiation and function, and mice lacking RORyt lack lymph nodes, Peyer's patches, and other organized GALT. In ILFs and cryptopatches, LTi-like cells are in close contact with different populations of intestinal dendritic cells (DCs), including a subpopulation recently shown to extend dendrites and sample luminal microflora. This interaction may allow for communication between the intestinal lumen and the immune cells in the lamina propria, which is necessary for maintaining homeostasis between the commensal microflora and the intestinal immune system. The potential functional implications of the organization of LTi-like cells, DCs, and lymphocytes in the lamina propria are discussed in the context of maintenance of homeostasis and of infectious diseases, particularly HIV infection.

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