Title | Anti-α4β7 therapy targets lymphoid aggregates in the gastrointestinal tract of HIV-1-infected individuals. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Uzzan, M, Tokuyama, M, Rosenstein, AK, Tomescu, C, SahBandar, IN, Ko, HM, Leyre, L, Chokola, A, Kaplan-Lewis, E, Rodriguez, G, Seki, A, Corley, MJ, Aberg, J, La Porte, A, Park, E-Y, Ueno, H, Oikonomou, I, Doron, I, Iliev, ID, Chen, BK, Lui, J, Schacker, TW, Furtado, GC, Lira, SA, Colombel, J-F, Horowitz, A, Lim, JK, Chomont, N, Rahman, AH, Montaner, LJ, Ndhlovu, LC, Mehandru, S |
Journal | Sci Transl Med |
Volume | 10 |
Issue | 461 |
Date Published | 2018 Oct 03 |
ISSN | 1946-6242 |
Abstract | Gut homing CD4 T cells expressing the integrin α4β7 are early viral targets and contribute to HIV-1 pathogenesis, likely by seeding the gastrointestinal (GI) tract with HIV. Although simianized anti-α4β7 monoclonal antibodies have shown promise in preventing or attenuating the disease course of simian immunodeficiency virus in nonhuman primate studies, the mechanisms of drug action remain elusive. We present a cohort of individuals with mild inflammatory bowel disease and concomitant HIV-1 infection receiving anti-α4β7 treatment. By sampling the immune inductive and effector sites of the GI tract, we have discovered that anti-α4β7 therapy led to a significant and unexpected attenuation of lymphoid aggregates, most notably in the terminal ileum. Given that lymphoid aggregates serve as important sanctuary sites for maintaining viral reservoirs, their attrition by anti-α4β7 therapy has important implications for HIV-1 therapeutics and eradication efforts and defines a rational basis for the use of anti-α4β7 therapy in HIV-1 infection. |
DOI | 10.1126/scitranslmed.aau4711 |
Alternate Journal | Sci Transl Med |
PubMed ID | 30282696 |
Grant List | R01 DK112296 / DK / NIDDK NIH HHS / United States S10 OD023547 / OD / NIH HHS / United States |