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Article: Gut-homing Δ42PD1+Vδ2 T cells promote innate mucosal damage via TLR4 during acute HIV type 1 infection

TitleGut-homing Δ42PD1+Vδ2 T cells promote innate mucosal damage via TLR4 during acute HIV type 1 infection
Authors
Issue Date2017
Citation
Nature Microbiology, 2017 How to Cite?
AbstractThe innate immune cells underlying mucosal inflammatory responses and damage during acute HIV-1 infection remain incompletely understood. Here, we report a Vδ2 subset of gut-homing γδ T cells with significantly upregulated Δ42PD1 (a PD1 isoform) in acute (~20%) HIV-1 patients compared to chronic HIV-1 patients (~11%) and healthy controls (~2%). The frequency of Δ42PD1+Vδ2 cells correlates positively with plasma levels of pro-inflammatory cytokines and fatty-acid-binding protein before detectable lipopolysaccharide in acute patients. The expression of Δ42PD1 can be induced by in vitro HIV-1 infection and is accompanied by high co-expression of gut-homing receptors CCR9/CD103. To investigate the role of Δ42PD1+Vδ2 cells in vivo, they were adoptively transferred into autologous humanized mice, resulting in small intestinal inflammatory damage, probably due to the interaction of Δ42PD1 with its cognate receptor Toll-like receptor 4 (TLR4). In addition, blockade of Δ42PD1 or TLR4 successfully reduced the cytokine effect induced by Δ42PD1+Vδ2 cells in vitro, as well as the mucosal pathological effect in humanized mice. Our findings have therefore uncovered a Δ42PD1–TLR4 pathway exhibited by virus-induced gut-homing Vδ2 cells that may contribute to innate immune activation and intestinal pathogenesis during acute HIV-1 infection. Δ 42PD1+Vδ2 cells may serve as a target for the investigation of diseases with mucosal inflammation.
Persistent Identifierhttp://hdl.handle.net/10722/247513

 

DC FieldValueLanguage
dc.contributor.authorCheung, KLA-
dc.contributor.authorKwok, HY-
dc.contributor.authorHuang, Y-
dc.contributor.authorChen, M-
dc.contributor.authorMo, Y-
dc.contributor.authorWU, X-
dc.contributor.authorLAM, KS-
dc.contributor.authorKong, H-
dc.contributor.authorLau, T.C.K.-
dc.contributor.authorZHOU, J-
dc.contributor.authorLi, J-
dc.contributor.authorCheng, L-
dc.contributor.authorLEE, BK-
dc.contributor.authorPeng, Q-
dc.contributor.authorLu, X-
dc.contributor.authorAn, M-
dc.contributor.authorWang, H-
dc.contributor.authorShang, H-
dc.contributor.authorZhou, B-
dc.contributor.authorWu, H-
dc.contributor.authorXu, A-
dc.contributor.authorYuen, KY-
dc.contributor.authorChen, Z-
dc.date.accessioned2017-10-18T08:28:27Z-
dc.date.available2017-10-18T08:28:27Z-
dc.date.issued2017-
dc.identifier.citationNature Microbiology, 2017-
dc.identifier.urihttp://hdl.handle.net/10722/247513-
dc.description.abstractThe innate immune cells underlying mucosal inflammatory responses and damage during acute HIV-1 infection remain incompletely understood. Here, we report a Vδ2 subset of gut-homing γδ T cells with significantly upregulated Δ42PD1 (a PD1 isoform) in acute (~20%) HIV-1 patients compared to chronic HIV-1 patients (~11%) and healthy controls (~2%). The frequency of Δ42PD1+Vδ2 cells correlates positively with plasma levels of pro-inflammatory cytokines and fatty-acid-binding protein before detectable lipopolysaccharide in acute patients. The expression of Δ42PD1 can be induced by in vitro HIV-1 infection and is accompanied by high co-expression of gut-homing receptors CCR9/CD103. To investigate the role of Δ42PD1+Vδ2 cells in vivo, they were adoptively transferred into autologous humanized mice, resulting in small intestinal inflammatory damage, probably due to the interaction of Δ42PD1 with its cognate receptor Toll-like receptor 4 (TLR4). In addition, blockade of Δ42PD1 or TLR4 successfully reduced the cytokine effect induced by Δ42PD1+Vδ2 cells in vitro, as well as the mucosal pathological effect in humanized mice. Our findings have therefore uncovered a Δ42PD1–TLR4 pathway exhibited by virus-induced gut-homing Vδ2 cells that may contribute to innate immune activation and intestinal pathogenesis during acute HIV-1 infection. Δ 42PD1+Vδ2 cells may serve as a target for the investigation of diseases with mucosal inflammation.-
dc.languageeng-
dc.relation.ispartofNature Microbiology-
dc.titleGut-homing Δ42PD1+Vδ2 T cells promote innate mucosal damage via TLR4 during acute HIV type 1 infection-
dc.typeArticle-
dc.identifier.emailCheung, KLA: allenc@hku.hk-
dc.identifier.emailKwok, HY: hauyeek@hku.hk-
dc.identifier.emailMo, Y: mophie@hku.hk-
dc.identifier.emailLi, J: joyli@hku.hk-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.authorityXu, A=rp00485-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authorityChen, Z=rp00243-
dc.identifier.doi10.1038/s41564-017-0006-5-
dc.identifier.hkuros280742-

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