Innate lymphoid cells in HIV pathogenesis and in the human female genital tract DOI
Alexandra Werner, Aleah Holmes,

Genna Moldovan

et al.

Current Opinion in HIV and AIDS, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Purpose of review Women are underrepresented in HIV infection and prevention research despite making up half people living with HIV. The female genital tract (FGT) serves as a primary site acquisition, but gaps knowledge remain regarding protective innate immune mechanisms. Innate lymphoid cells tissue-resident involved mucosal barrier maintenance protection, (ILCs) altered during chronic infection. However, ILCs role pathogenesis is unclear they poorly characterized the FGT. Recent findings Human differ from their mouse counterparts plastically adjust to tissue residency. ILC characterization difficult due tissue-specific adaptations transition between subsets. While evidence for involvement antiviral activity provided models, human immunity understudied, particularly In HIV/simian immunodeficiency virus (SIV) infection, manner, SIV models indicate potential responses. Summary plastic that provide protection at surfaces display capacity. Considering primarily transmitted through exposure, more needed understand contribution relevant acquisition.

Language: Английский

The multifaceted roles of B lymphocytes in metabolic dysfunction–associated steatotic liver disease DOI Creative Commons
Huige Li, Ning Xia

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 20, 2024

Recent evidence suggests that adaptive immune cells are important contributors to metabolic dysfunction–associated steatotic liver disease (MASLD, formerly non-alcoholic fatty disease, NAFLD). In biopsies from MASLD patients, the accumulation of intrahepatic B is positively correlated with activity score. Hepatic B-cell infiltration observed in experimental models dysfunction-associated steatohepatitis (MASH, steatohepatitis, NASH). Intrahepatic B2 have been shown contribute MASLD/MASH by activating T cells, macrophages and hepatic stellate producing pathogenic IgG antibodies. mice fed a MASH diet, selective depletion reduces fibrosis. Intestinal metabolically activated promote T-cell activation independently TCR signaling. addition, fibrosis monocyte-derived through secretion IgA immunoglobulins. Furthermore, our recent study indicates certain cell subsets, very likely regulatory may play protective role MASLD. This review summarizes molecular mechanisms functions discusses future research directions on different roles MASH.

Language: Английский

Citations

3
DNMT1 inhibition reprograms T cells to NK-like cells with potent antitumor activity DOI
Yao Li, Jiongliang Wang,

Linfu Zhou

et al.

Science Immunology, Journal Year: 2025, Volume and Issue: 10(105)

Published: March 21, 2025

Inactivation of the transcription factor BCL11B reprograms T cells into induced-T-to-NK (ITNKs). However, it remains unclear how suppresses natural killer (NK) cell transcriptional programs. Here, we identified that DNA methyltransferase DNMT1 physically interacts with BCL11B, increasing stability and fidelity methylation maintenance for NK cell–related genes, thereby repressing their expression. Moreover, maintains epigenetic silencing a distinct subset genes independent BCL11B. inhibition or depletion chimeric antigen receptor (CAR)–T NK-like exhibit more robust antitumor effects than BCL11B-deficient ITNKs parental CAR-T cells. H3K27me3 (trimethylation histone 3 lysine 27) synergizes to repress pathways, combined EZH2 (enhancer zeste homolog 2) potentiates both reprogramming cytotoxicity Our findings uncover molecular mechanisms safeguard identity provide rationale deriving inhibitors cancer immunotherapy.

Language: Английский

Citations

0
Single-cell profiling aligns CD56bright and cytomegalovirus-induced adaptive natural killer cells to a naïve-memory relationship DOI Creative Commons
M. Kazim Panjwani, Simon Grassmann, Rosa Sottile

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 17, 2024

Development of antigen-specific memory upon pathogen exposure is a hallmark the adaptive immune system. While natural killer (NK) cells are considered part innate system, humans exposed to chronic viral cytomegalovirus (CMV) often possess distinct NK cell population lacking in individuals who have not been exposed, termed "adaptive" cells. To identify "naïve" from which this "memory" derives, we performed phenotypic, transcriptional, and functional profiling subsets. We identified immature precursors Adaptive that equally present both CMV+ CMV- individuals, resolved an transcriptional state most mature sharing common gene program with CD56

Language: Английский

Citations

1
Chameleon impersonation of NK cells and ILC1s DOI
M. Zeeshan Chaudhry, Gabrielle T. Belz

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(8), P. 1313 - 1315

Published: July 9, 2024

Language: Английский

Citations

1
Ex vivo Model of Functioning Human Lymph Node Reveals Pivotal Role for Innate Lymphoid Cells and Stromal Populations in Response to Vaccine Adjuvant DOI Open Access
Joannah R. Fergusson, Jacqueline H.Y. Siu,

Nitya Gupta

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 22, 2024

Immunological processes that underpin the administration of therapeutics and vaccines are poorly defined due to a lack models which faithfully recapitulate human immune responses. Inbred mice diversity inherent people, while microanatomical organisation tissue is lost in isolated cell suspensions. We describe precision-cut lymph node (LN) slices as architecturally-preserved, functioning lymphoid model system, explore early inflammatory responses potent vaccine liposomal adjuvant containing TLR4-agonist QS21 saponin. Combining scRNA-seq, multiplexed immunofluorescence secretome analysis, we dissect direct indirect signalling pathways both leukocytes stromal cells reveal communication networks linking innate adaptive immunity. Application molecular inhibitors reveals secretion IL- 1b, but not IL-18, TLR4-dependent LN. Retaining donor-to-donor variation, this ex vivo LN system enables study previously difficult observe humans, paving way towards precision medicine.

Language: Английский

Citations

0
The multifaceted roles of TCF1 in innate and adaptive lymphocytes DOI
Matthew McCullen, Eugene M. Oltz

Advances in immunology, Journal Year: 2024, Volume and Issue: unknown, P. 39 - 71

Published: Jan. 1, 2024

Language: Английский

Citations

0
Group 3 Innate Lymphoid Cells: A Potential Therapeutic Target for Steroid Resistant Asthma DOI Creative Commons

Marzhan Berkinbayeva,

Wenjing Gu, Zhifeng Chen

et al.

Clinical Reviews in Allergy & Immunology, Journal Year: 2024, Volume and Issue: 68(1)

Published: Dec. 27, 2024

Asthma is a chronic airway inflammatory disease that affects millions globally. Although glucocorticoids are mainstay of asthma treatment, subset patients show resistance to these therapies, resulting in poor control and increased morbidity. The complex mechanisms underlying steroid-resistant (SRA) involve Th1 Th17 lymphocyte activity, neutrophil recruitment, NLRP3 inflammasome activation. Recent studies provided evidence innate lymphoid cells type 3 (ILC3s) might be potential therapeutic targets for non-eosinophilic (NEA) SRA. Like cells, ILC3s play crucial roles immune responses, inflammation, tissue homeostasis, contributing severity corticosteroid NEA. Biologics targeting ILC3-related pathways have shown promise managing Th2-low asthma, suggesting new avenues SRA treatment. This review aims explore the risk factors SRA, discuss challenges consolidate current findings on elucidate their role respiratory conditions. We present latest involvement human diseases development. Furthermore, we emerging biologics NEA highlights challenges, strategies, addresses significant gap research, with implications improving management asthma.

Language: Английский

Citations

0
Innate lymphoid cells in HIV pathogenesis and in the human female genital tract DOI
Alexandra Werner, Aleah Holmes,

Genna Moldovan

et al.

Current Opinion in HIV and AIDS, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Purpose of review Women are underrepresented in HIV infection and prevention research despite making up half people living with HIV. The female genital tract (FGT) serves as a primary site acquisition, but gaps knowledge remain regarding protective innate immune mechanisms. Innate lymphoid cells tissue-resident involved mucosal barrier maintenance protection, (ILCs) altered during chronic infection. However, ILCs role pathogenesis is unclear they poorly characterized the FGT. Recent findings Human differ from their mouse counterparts plastically adjust to tissue residency. ILC characterization difficult due tissue-specific adaptations transition between subsets. While evidence for involvement antiviral activity provided models, human immunity understudied, particularly In HIV/simian immunodeficiency virus (SIV) infection, manner, SIV models indicate potential responses. Summary plastic that provide protection at surfaces display capacity. Considering primarily transmitted through exposure, more needed understand contribution relevant acquisition.

Language: Английский

Citations

0