Interferon subverts an AHR-JUN axis to promote CXCL13 T cells in lupus.

Systemic lupus erythematosus (SLE) is prototypical autoimmune disease driven by pathological T cell-B cell interactions. Expansion of T follicular helper (T) and T peripheral helper (T) cells, two T cell populations that provide help to B cells, is a prominent feature of SLE. Human T and T cells characteristically produce high levels of the B cell chemoattractant CXCL13 (refs.

RALDH Activity Induced by Bacterial/Fungal Pathogens in CD16 Monocyte-Derived Dendritic Cells Boosts HIV Infection and Outgrowth in CD4 T Cells.

HIV reservoirs persist in gut-homing CD4 T cells of people living with HIV and receiving antiretroviral therapy, but the antigenic specificity of such reservoirs remains poorly documented. The imprinting for gut homing is mediated by retinoic acid (RA), a vitamin A-derived metabolite produced by dendritic cells (DCs) exhibiting RA-synthesizing (RALDH) activity. RALDH activity in DCs can be induced by TLR2 ligands, such as bacterial peptidoglycans and fungal zymosan.

Improving HIV Outgrowth by Optimizing Cell-Culture Conditions and Supplementing With Retinoic Acid.

The persistence of replication-competent HIV reservoirs in people living with HIV (PLWH) receiving antiretroviral therapy (ART) is a barrier to cure. Therefore, their accurate quantification is essential for evaluating the efficacy of new therapeutic interventions and orienting the decision to interrupt ART. Quantitative viral outgrowth assays (QVOAs) represent the "" for measuring the size of replication-competent HIV reservoirs.

CD16 monocytes give rise to CD103RALDH2TCF4 dendritic cells with unique transcriptional and immunological features.

Classical CD16 vs intermediate/nonclassical CD16 monocytes differ in their homing potential and biological functions, but whether they differentiate into dendritic cells (DCs) with distinct contributions to immunity against bacterial/viral pathogens remains poorly investigated. Here, we employed a systems biology approach to identify clinically relevant differences between CD16 and CD16 monocyte-derived DCs (MDDCs). Although both CD16 and CD16 MDDCs acquire classical immature/mature DC markers in vitro, genome-wide transcriptional profiling revealed unique molecular signatures for CD16 MDDCs, including adhesion molecules (ITGAE/CD103), transcription factors (TCF7L2/TCF4), and enzymes (ALDH1A2/RALDH2), whereas CD16 MDDCs exhibit a CDH1/E-cadherin phenotype.

The Biology of Monocytes and Dendritic Cells: Contribution to HIV Pathogenesis.

Myeloid cells such as monocytes, dendritic cells (DC) and macrophages (MΦ) are key components of the innate immune system contributing to the maintenance of tissue homeostasis and the development/resolution of immune responses to pathogens. Monocytes and DC, circulating in the blood or infiltrating various lymphoid and non-lymphoid tissues, are derived from distinct bone marrow precursors and are typically short lived. Conversely, recent studies revealed that subsets of tissue resident MΦ are long-lived as they originate from embryonic/fetal precursors that have the ability to self-renew during the life of an individual.

New insights into the heterogeneity of Th17 subsets contributing to HIV-1 persistence during antiretroviral therapy.

Background: Th17 cells are permissive to HIV-1 infection and their depletion from the gut of infected individuals leads to microbial translocation, a major cause for non-AIDS co-morbidities. Most recent evidence supports the contribution of long-lived Th17 cells to HIV persistence during antiretroviral therapy (ART). However, the identity of long-lived Th17 cells remains unknown.

Identification of novel HIV-1 dependency factors in primary CCR4(+)CCR6(+)Th17 cells via a genome-wide transcriptional approach.

Background: The HIV-1 infection is characterized by profound CD4(+) T cell destruction and a marked Th17 dysfunction at the mucosal level. Viral suppressive antiretroviral therapy restores Th1 but not Th17 cells. Although several key HIV dependency factors (HDF) were identified in the past years via genome-wide siRNA screens in cell lines, molecular determinants of HIV permissiveness in primary Th17 cells remain to be elucidated.

Impaired Th17 polarization of phenotypically naive CD4(+) T-cells during chronic HIV-1 infection and potential restoration with early ART.

Background: Depletion of mucosal Th17 cells during HIV/SIV infections is a major cause for microbial translocation, chronic immune activation, and disease progression. Mechanisms contributing to Th17 deficit are not fully elucidated. Here we investigated alterations in the Th17 polarization potential of naive-like CD4(+) T-cells, depletion of Th17-commited subsets during HIV pathogenesis, and Th17 restoration in response to antiretroviral therapy (ART).

Transcriptional profiling reveals molecular signatures associated with HIV permissiveness in Th1Th17 cells and identifies peroxisome proliferator-activated receptor gamma as an intrinsic negative regulator of viral replication.

Background: We previously demonstrated that primary Th1Th17 cells are highly permissive to HIV-1, whereas Th1 cells are relatively resistant. Molecular mechanisms underlying these differences remain unknown.

Results: Exposure to replication competent and single-round VSV-G pseudotyped HIV strains provide evidence that superior HIV replication in Th1Th17 vs.

The colocalization potential of HIV-specific CD8+ and CD4+ T-cells is mediated by integrin β7 but not CCR6 and regulated by retinoic acid.

CD4(+) T-cells from gut-associated lymphoid tissues (GALT) are major targets for HIV-1 infection. Recruitment of excess effector CD8(+) T-cells in the proximity of target cells is critical for the control of viral replication. Here, we investigated the colocalization potential of HIV-specific CD8(+) and CD4(+) T-cells into the GALT and explored the role of retinoic acid (RA) in regulating this process in a cohort of HIV-infected subjects with slow disease progression.

Memory CCR6+CD4+ T cells are preferential targets for productive HIV type 1 infection regardless of their expression of integrin β7.

HIV type 1 infection is associated with a rapid depletion of Th17 cells from the GALT. The chemokine receptor CCR6 is a marker for Th17 lineage polarization and HIV permissiveness in memory CD4(+) T cells. CCR6(+) T cells have the potential to migrate into the GALT via the gut-homing integrin α(4)β(7), a newly identified HIV-gp120 binding receptor.

Transcriptional profiling reveals developmental relationship and distinct biological functions of CD16+ and CD16- monocyte subsets.

Background: Human peripheral blood monocytes (Mo) consist of subsets distinguished by expression of CD16 (FCgammaRIII) and chemokine receptors. Classical CD16- Mo express CCR2 and migrate in response to CCL2, while a minor CD16+ Mo subset expresses CD16 and CX3CR1 and migrates into tissues expressing CX3CL1. CD16+ Mo produce pro-inflammatory cytokines and are expanded in certain inflammatory conditions including sepsis and HIV infection.