Pathogens
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2021
·Vol. 11
·期 1
·7
·
IF 3.492
Fuchun Zhang,Lingling Sun,Mark K. Lafferty,Joseph B. Margolick,Alfredo Garzino-Demo
CD4+CCR6+T cells are highly susceptible to HIV infection, and a high cytokine producing CCR6+T cell subset is selectively lost during HIV infection. The CCR6 chemokine MIP-3α (CCL20) is produced at sites of infection in SIV animal models. Recently, we have shown that MIP-3α inhibits HIV replication. This inhibition of HIV infection is mediated by CCR6 signaling and eventuates in increased APOBEC3G expression. Since there are few existing reports on the role of MIP-3α in health or disease, we studied its production by PBMCs from HIV-seronegative and HIV+ subjects. We evaluated the ability of PBMCs to produce MIP-3α in response to antigen stimulation using cells obtained from two groups: one composed of HIV-seronegative subjects (n = 16) and the other composed of HIV+ subjects (n = 58), some asymptomatic and some with clinically defined AIDS. Antigens included fragment C of the tetanus toxin,Candida albicans, whole-inactivated HIV, and HIV p24. MIP-3α was detected by ELISA in tissue culture supernatants of antigen-stimulated PBMCs. MIP-3α production by antigen-stimulated PBMCs was readily measured for HIV-negative subjects and for HIV-seropositive asymptomatic subjects, but not for patients with AIDS. These results suggest that subversion of the MIP-3α-CCR6 axis by HIV during the course of infection contributes to the loss of immune function that eventually leads to AIDS.Keywords:CCR6;MIP-3α;immune response;antigen stimulation;Th17
研究领域:
免疫学
·
病毒学
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DOI
PubMed
高影响因子
CANCER LETTERS
·
2026
·
IF 11.8
Ling-Dong Meng,Lu-Yang Jiang,Yang-Yang Liang,Zhan-Zhong Zheng,Qun Chen,Dan-Rui Li,Shuang Wang,Hao Yuan,Xu Feng,Kui-Rong Jiang
Pancreatic cancer has a dismal prognosis, largely due to resistance to all current therapeutic modalities, including prevailing immunotherapy. Deciphering the mechanisms underlying the immunosuppressive tumor microenvironment is pivotal for developing effective therapeutic strategies. In this study, we found that the expression of CCL20 is negatively correlated with the infiltration of CD8 + T cells, and consistently, patients with higher CCL20 expression have a worse prognosis. CCL20, as a secreted ligand protein regulated by SP5, can bind to its cognate receptor CCR6 in the tumor microenvironment and is mainly produced by tumor cells, as confirmed by single-cell RNA sequencing and immunofluorescence staining of tumor tissues. Compared with CCL20 wild-type tumors, CCL20 knockout tumors exhibited impaired growth, decreased infiltration of CCR6 + Tregs, and concomitantly increased infiltration of CD8 + T cells. Importantly, this altered immune infiltration phenotype was abolished in Treg-specific CCR6 knockout mice. Furthermore, CCR6 inhibition potentiated the efficacy of anti-PD1 immune checkpoint blockade. Taken together, our data demonstrate that tumor cell-derived CCL20 shapes an immunosuppressive microenvironment in pancreatic cancer by recruiting CCR6 + Tregs, suggesting that targeting the CCL20-CCR6 axis offers a promising therapeutic strategy, particularly when combined with immune checkpoint blockade.
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高影响因子
Nature Communications
·
2026
·
IF 18.1
Junyu He,Meiqi Chen,Laiqin Peng,Qiqiong Wang,Yizhuang Lu,Yimin Chen,Xinyao Li,Yanling Mou,Jianjun Wang,Yuxiong Guo,Kai Wu,Yumei He
Group 3 innate lymphoid cells (ILC3) are crucial in neonatal necrotizing enterocolitis (NEC); however, the underlying mechanisms remain elusive. Here, we identify NKp46⁻CCR6⁻ (double-negative, DN) ILC3s as the dominant pathogenic subset driving NEC via IL-17 A secretion, which disrupts intestinal barrier integrity. Mechanistically, Atg5 activates autophagy in DN ILC3s during NEC. Atg5 conditional knockout in RORγt⁺ cells mitigates NEC, reduces DN ILC3 accumulation and IL-17 A production. Atg5 deficiency also decreases HIF-1α chromatin accessibility and transcriptional activity, shifting DN ILC3 metabolism from glycolysis to fatty acid oxidation. Lipidomics reveals phosphatidylcholine as a key downstream metabolite of Atg5-mediated autophagy. Phosphatidylcholine supplementation suppresses DN ILC3-driven inflammation, restores metabolic homeostasis, elevates Clostridium abundance, and ameliorates NEC in mice. Importantly, human NEC tissues exhibit increased ILC3 proportions, autophagic activity, and IL-17 A/IL-22 secretion. Thus, we uncover an Atg5–autophagy–glycolipid metabolic axis in DN ILC3s that drives NEC pathogenesis, providing a promising therapeutic target for neonatal NEC. Group 3 innate lymphoid cells (ILC3s) are key regulator of intestinal immunity. However, whether these cells drive necrotizing enterocolitis (NEC) and through which mechanism remains unexplored. Here, the authors employ a mouse model of neonatal NEC and implicate NKp46⁻CCR6⁻ double negative ILC3 autophagy in pathogenic ILC3 expansion and activation during NEC via HIF1a-modulation of glycolipid metabolism.
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高影响因子
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