Integrin α4β7 Blockade Preferentially Impacts CCR6+ Lymphocyte Subsets in Blood and Mucosal Tissues of Naive Rhesus Macaques. 2018

Giulia Calenda, and Rassamon Keawvichit, and Géraldine Arrode-Brusés, and Kovit Pattanapanyasat, and Ines Frank, and Siddappa N Byrareddy, and James Arthos, and Claudia Cicala, and Brooke Grasperge, and James L Blanchard, and Agegnehu Gettie, and Keith A Reimann, and Aftab A Ansari, and Elena Martinelli
Center for Biomedical Research, Population Council, New York, NY 10065.

Infusion of a simianized anti-α4β7 mAb (Rh-α4β7) just before and following SIV infection protected rhesus macaques from developing AIDS and partially from vaginal SIV acquisition. Recently, short-term treatment with Rh-α4β7 in combination with cART was found to lead to prolonged viral suppression after withdrawal of all therapeutic interventions. The humanized form of Rh-α4β7, vedolizumab, is a highly effective treatment for inflammatory bowel disease. To clarify the mechanism of action of Rh-α4β7, naive macaques were infused with Rh-α4β7 and sampled in blood and tissues before and after treatment to monitor several immune cell subsets. In blood, Rh-α4β7 increased the CD4+ and CD8+ T cell counts, but not B cell counts, and preferentially increased CCR6+ subsets while decreasing CD103+ and CD69+ lymphocytes. In mucosal tissues, surprisingly, Rh-α4β7 did not impact integrin α4+ cells, but decreased the frequencies of CCR6+ and CD69+ CD4+ T cells and, in the gut, Rh-α4β7 transiently decreased the frequency of memory and IgA+ B cells. In summary, even in the absence of inflammation, Rh-α4β7 impacted selected immune cell subsets in different tissues. These data provide new insights into the mechanisms by which Rh-α4β7 may mediate its effect in SIV-infected macaques with implications for understanding the effect of treatment with vedolizumab in patients with inflammatory bowel disease.

UI MeSH Term Description Entries
D008253 Macaca mulatta A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans. Chinese Rhesus Macaques,Macaca mulatta lasiota,Monkey, Rhesus,Rhesus Monkey,Rhesus Macaque,Chinese Rhesus Macaque,Macaca mulatta lasiotas,Macaque, Rhesus,Rhesus Macaque, Chinese,Rhesus Macaques,Rhesus Macaques, Chinese,Rhesus Monkeys
D009092 Mucous Membrane An EPITHELIUM with MUCUS-secreting cells, such as GOBLET CELLS. It forms the lining of many body cavities, such as the DIGESTIVE TRACT, the RESPIRATORY TRACT, and the reproductive tract. Mucosa, rich in blood and lymph vessels, comprises an inner epithelium, a middle layer (lamina propria) of loose CONNECTIVE TISSUE, and an outer layer (muscularis mucosae) of SMOOTH MUSCLE CELLS that separates the mucosa from submucosa. Lamina Propria,Mucosa,Mucosal Tissue,Muscularis Mucosae,Mucous Membranes,Membrane, Mucous,Membranes, Mucous,Mucosae, Muscularis,Mucosal Tissues,Propria, Lamina,Tissue, Mucosal,Tissues, Mucosal
D009928 Organ Specificity Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen. Tissue Specificity,Organ Specificities,Specificities, Organ,Specificities, Tissue,Specificity, Organ,Specificity, Tissue,Tissue Specificities
D003713 Dendritic Cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION). Dendritic Cells, Interdigitating,Interdigitating Cells,Plasmacytoid Dendritic Cells,Veiled Cells,Dendritic Cells, Interstitial,Dendritic Cells, Plasmacytoid,Interdigitating Dendritic Cells,Interstitial Dendritic Cells,Cell, Dendritic,Cell, Interdigitating,Cell, Interdigitating Dendritic,Cell, Interstitial Dendritic,Cell, Plasmacytoid Dendritic,Cell, Veiled,Cells, Dendritic,Cells, Interdigitating,Cells, Interdigitating Dendritic,Cells, Interstitial Dendritic,Cells, Plasmacytoid Dendritic,Cells, Veiled,Dendritic Cell,Dendritic Cell, Interdigitating,Dendritic Cell, Interstitial,Dendritic Cell, Plasmacytoid,Interdigitating Cell,Interdigitating Dendritic Cell,Interstitial Dendritic Cell,Plasmacytoid Dendritic Cell,Veiled Cell
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015496 CD4-Positive T-Lymphocytes A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
D016023 Integrins A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors (RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation. Integrin
D016131 Lymphocyte Subsets A classification of lymphocytes based on structurally or functionally different populations of cells. Lymphocyte Subpopulations,Lymphocyte Subpopulation,Lymphocyte Subset,Subpopulation, Lymphocyte,Subpopulations, Lymphocyte,Subset, Lymphocyte,Subsets, Lymphocyte
D054399 Receptors, CCR6 CCR receptors with specificity for CHEMOKINE CCL20. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS. Antigens, CD196,CC Chemokine Receptor 6,CCR6 Receptors,CD196 Antigens,CC Chemokine Receptors 6

Related Publications

Giulia Calenda, and Rassamon Keawvichit, and Géraldine Arrode-Brusés, and Kovit Pattanapanyasat, and Ines Frank, and Siddappa N Byrareddy, and James Arthos, and Claudia Cicala, and Brooke Grasperge, and James L Blanchard, and Agegnehu Gettie, and Keith A Reimann, and Aftab A Ansari, and Elena Martinelli
February 2021, FASEB journal : official publication of the Federation of American Societies for Experimental Biology,
Giulia Calenda, and Rassamon Keawvichit, and Géraldine Arrode-Brusés, and Kovit Pattanapanyasat, and Ines Frank, and Siddappa N Byrareddy, and James Arthos, and Claudia Cicala, and Brooke Grasperge, and James L Blanchard, and Agegnehu Gettie, and Keith A Reimann, and Aftab A Ansari, and Elena Martinelli
August 2020, Science advances,
Giulia Calenda, and Rassamon Keawvichit, and Géraldine Arrode-Brusés, and Kovit Pattanapanyasat, and Ines Frank, and Siddappa N Byrareddy, and James Arthos, and Claudia Cicala, and Brooke Grasperge, and James L Blanchard, and Agegnehu Gettie, and Keith A Reimann, and Aftab A Ansari, and Elena Martinelli
October 2010, Inflammatory bowel diseases,
Giulia Calenda, and Rassamon Keawvichit, and Géraldine Arrode-Brusés, and Kovit Pattanapanyasat, and Ines Frank, and Siddappa N Byrareddy, and James Arthos, and Claudia Cicala, and Brooke Grasperge, and James L Blanchard, and Agegnehu Gettie, and Keith A Reimann, and Aftab A Ansari, and Elena Martinelli
February 2011, Journal of medical primatology,
Giulia Calenda, and Rassamon Keawvichit, and Géraldine Arrode-Brusés, and Kovit Pattanapanyasat, and Ines Frank, and Siddappa N Byrareddy, and James Arthos, and Claudia Cicala, and Brooke Grasperge, and James L Blanchard, and Agegnehu Gettie, and Keith A Reimann, and Aftab A Ansari, and Elena Martinelli
April 2001, Developmental and comparative immunology,
Giulia Calenda, and Rassamon Keawvichit, and Géraldine Arrode-Brusés, and Kovit Pattanapanyasat, and Ines Frank, and Siddappa N Byrareddy, and James Arthos, and Claudia Cicala, and Brooke Grasperge, and James L Blanchard, and Agegnehu Gettie, and Keith A Reimann, and Aftab A Ansari, and Elena Martinelli
November 1992, Laboratory investigation; a journal of technical methods and pathology,
Giulia Calenda, and Rassamon Keawvichit, and Géraldine Arrode-Brusés, and Kovit Pattanapanyasat, and Ines Frank, and Siddappa N Byrareddy, and James Arthos, and Claudia Cicala, and Brooke Grasperge, and James L Blanchard, and Agegnehu Gettie, and Keith A Reimann, and Aftab A Ansari, and Elena Martinelli
October 2000, European journal of haematology,
Giulia Calenda, and Rassamon Keawvichit, and Géraldine Arrode-Brusés, and Kovit Pattanapanyasat, and Ines Frank, and Siddappa N Byrareddy, and James Arthos, and Claudia Cicala, and Brooke Grasperge, and James L Blanchard, and Agegnehu Gettie, and Keith A Reimann, and Aftab A Ansari, and Elena Martinelli
May 2019, PLoS pathogens,
Giulia Calenda, and Rassamon Keawvichit, and Géraldine Arrode-Brusés, and Kovit Pattanapanyasat, and Ines Frank, and Siddappa N Byrareddy, and James Arthos, and Claudia Cicala, and Brooke Grasperge, and James L Blanchard, and Agegnehu Gettie, and Keith A Reimann, and Aftab A Ansari, and Elena Martinelli
January 1988, Human immunology,
Giulia Calenda, and Rassamon Keawvichit, and Géraldine Arrode-Brusés, and Kovit Pattanapanyasat, and Ines Frank, and Siddappa N Byrareddy, and James Arthos, and Claudia Cicala, and Brooke Grasperge, and James L Blanchard, and Agegnehu Gettie, and Keith A Reimann, and Aftab A Ansari, and Elena Martinelli
February 2012, Parasitology research,
Copied contents to your clipboard!