caa a22 4500 467906882 CHVBK 20180406152836.0 cr unu---uuuuu 170328e20060901xx s 000 0 eng 10.1007/s00251-006-0138-x doi (NATIONALLICENCE)springer-10.1007/s00251-006-0138-x Formation of B and T cell subsets require the cannabinoid receptor CB2 [Elektronische Daten] [David Ziring, Bo Wei, Peter Velazquez, Matthew Schrage, Nancy Buckley, Jonathan Braun] A recent and surprising body of research has linked changes in immune function to biologic and therapeutic targeting of cannabinoid receptors, which prototypically respond to delta-9 tetrahydrocannabinol. The peripheral cannabinoid receptor CB2 is highly expressed in immune cell types (macrophages, dendritic cells, and B cells), and pharmacologically alters their cytokine production and responsiveness. Accordingly, cannabinoid agonists can powerfully alter susceptibility to certain microbial infections, atherosclerosis, and cancer immunotherapy. What is unknown is the physiologic role of natural levels of endocannabinoids and their receptors in normal immune homeostasis. Gαi2−/− mice are deficient in the formation of certain B and T cell subsets and are susceptible to immune dysregulation, notably developing inflammatory bowel disease. A key issue is the identity of the Gi-coupled receptors relevant to this Gαi2-signaling pathway. We find that mice deficient in CB2, the Gi-coupled peripheral endocannabinoid receptor, have profound deficiencies in splenic marginal zone, peritoneal B1a cells, splenic memory CD4+ T cells, and intestinal natural killer cells and natural killer T cells. These findings partially phenocopy and extend the lymphocyte developmental disorder associated with the Gαi2−/− genotype, and suggest that the endocannabinoid system is required for the formation of T and B cell subsets involved in immune homeostasis. This noncompensatable requirement for physiologic function of the endocannabinoid system is novel. Because levels of endocannabinoids are highly restricted microanatomically, local regulation of their production and receptor expression offers a new principle for regional immune homeostasis and disease susceptibility, and extends and refines the rationale for CB2-targeted immunotherapy in immune and inflammatory diseases. Springer-Verlag, 2006 CB2 nationallicence Endocannabinoid nationallicence B cell development nationallicence NKT lymphocytes nationallicence NK cells nationallicence Ziring David Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, 90095, Los Angeles, CA, USA aut Wei Bo Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, 90095, Los Angeles, CA, USA aut Velazquez Peter Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, 90095, Los Angeles, CA, USA aut Schrage Matthew Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, 90095, Los Angeles, CA, USA aut Buckley Nancy Department of Biological Sciences, California State Polytechnic University, 91768, Pomona, CA, USA aut Braun Jonathan Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, 90095, Los Angeles, CA, USA aut Immunogenetics Springer-Verlag 58/9(2006-09-01), 714-725 0093-7711 58:9<714 2006 58 251 https://doi.org/10.1007/s00251-006-0138-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00251-006-0138-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ziring David Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, 90095, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Wei Bo Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, 90095, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Velazquez Peter Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, 90095, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Schrage Matthew Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, 90095, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Buckley Nancy Department of Biological Sciences, California State Polytechnic University, 91768, Pomona, CA, USA aut NATIONALLICENCE 700 1- Braun Jonathan Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, 90095, Los Angeles, CA, USA aut NATIONALLICENCE 773 0- Immunogenetics Springer-Verlag 58/9(2006-09-01), 714-725 0093-7711 58:9<714 2006 58 251 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer