The main goal of this program is to conduct a novel analysis of lymphocyte and innate lymphoid cell populations in human lymphoid and mucosal tissues in steady state and in organ transplantation, to elucidate novel aspects of human immune responses in the whole body that have not previously been explored. We will use two sources of human tissues for this program: deceased organ donors and transplant patients. Projects 1-3 will examine T, B and innate lymphoid cells (ILC) in multiple tissues obtained from . organ donors, and Project 4 will characterize lymphocyte and ILC populations in intestinal transplants. For all of the projects, the acquisition of human tissues is essential. The human tissue and sample acquisition core will be responsible for coordinating all ofthe personnel, institutional assurance, protocols and MTAs necessary to acquire and process human tissues, and distribute samples to all four projects. This core will function for all years of the project as it is essential to the entire program. This essential core will be divided into two parts based on the two main sources of human tissue samples. In the first part, the core will obtain and process multiple lymphoid and mucosal tissues from human organ donors. We have established the necessary protocols and collaborations with CUMC surgeons and the New York Organ Donor network (NYODN) to obtain from research-consented organ donors, tissues that are not used for life-saving transplantation. For this part of the core, we will coordinate the acquisition of multiple lymphoid tissues and mucosal tissues from organ donors whose next-of-kin have consented for use of tissues for research. The tissues will be processed in the laboratory and cell suspensions, whole tissues and tissue mounts will be distributed to all project laboratories (Projects 1-4). For the second part ofthe core, we will coordinate the acquisition of biopsy and peripheral blood samples from transplant patients. We will obtain biopsy and peripheral blood specimens from intestinal transplant patients who will be enrolled in studies related to Project 4. The personnel in this core will maintain IRB protocols for obtaining samples, enroll patients in this study, will work with the clinicians to obtain biopsy and blood samples as part of their clinical management, coordinate their distribution to Project 4 investigators for the characterization of T cell reconstitufion and alloreactivity, and to the CCTI Biobank for processing and storage.

Public Health Relevance

This novel research program in human immunology is centered upon a novel resource of human tissue acquisition from organ donors. The acquisition of multiple human lymphoid and mucosal tissues from organ donors in collaboration with the NYODN, and the enrollment and acquisition of samples from intestinal transplant patients will be organized and coordinated by this core for distribution to all project investigators.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Special Emphasis Panel (ZAI1-QV-I)
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Columbia University
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Monticelli, Laurel A; Buck, Michael D; Flamar, Anne-Laure et al. (2016) Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation. Nat Immunol 17:656-65
Rak, Gregory D; Osborne, Lisa C; Siracusa, Mark C et al. (2016) IL-33-Dependent Group 2 Innate Lymphoid Cells Promote Cutaneous Wound Healing. J Invest Dermatol 136:487-96
Thome, Joseph J C; Bickham, Kara L; Ohmura, Yoshiaki et al. (2016) Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues. Nat Med 22:72-7
Murray, Alexandra J; Kwon, Kyungyoon J; Farber, Donna L et al. (2016) The Latent Reservoir for HIV-1: How Immunologic Memory and Clonal Expansion Contribute to HIV-1 Persistence. J Immunol 197:407-17
Farber, Donna L; Netea, Mihai G; Radbruch, Andreas et al. (2016) Immunological memory: lessons from the past and a look to the future. Nat Rev Immunol 16:124-8
DeWolf, Susan; Shen, Yufeng; Sykes, Megan (2016) A New Window into the Human Alloresponse. Transplantation 100:1639-49
Weiner, Joshua; Zuber, Julien; Shonts, Brittany et al. (2016) Long-Term Persistence of Innate Lymphoid Cells in the Gut After Intestinal Transplantation. Transplantation :
Tait Wojno, Elia D; Artis, David (2016) Emerging concepts and future challenges in innate lymphoid cell biology. J Exp Med 213:2229-2248
Sonnenberg, Gregory F; Artis, David (2015) Innate lymphoid cells in the initiation, regulation and resolution of inflammation. Nat Med 21:698-708
Monticelli, Laurel A; Osborne, Lisa C; Noti, Mario et al. (2015) IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions. Proc Natl Acad Sci U S A 112:10762-7

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