Human lung-resident mucosal-associated invariant T cells are abundant, express antimicrobial proteins, and are cytokine responsive

Meermeier, Erin W.; Zheng, Christina; Tran, Jessica; Soma, Shogo; Worley, Aneta; Weiss, David I.; Modlin, Robert L.; Swarbrick, Gwendolyn; Karamooz, Elham; Khuzwayo, Sharon; Wong, Emily; Gold, Marielle C.; Lewinsohn, David

doi:10.1038/s42003-022-03823-w

Cited by 21 publications

(14 citation statements)

References 58 publications

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“…is the expression of the NK receptor KLRB1. These findings closely align with previously identified markers associated with human MAIT and Vd2g9 + gd T cells (Davey et al, 2018;Meermeier et al, 2022;Park et al, 2019) 12), is characterized by increased expression of CX3CR1 (Supplementary Figure 13). The graded expression of CX3CR1 correlates with the differentiation of both CD4 and CD8 T cells towards an effector state (Zwijnenburg et al, 2023).…”

Section: Gene Expressionsupporting

confidence: 90%

Unraveling the Phenotypic States of Human innate-like T Cells: Comparative Insights with Conventional T Cells and Mouse Models

Loh,

Carcy,

Krovi

et al. 2023

Preprint

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The “innate-like” T cell compartment, known as Tinn, represents a diverse group of T cells that straddle the boundary between innate and adaptive immunity, having the ability to mount rapid responses following activation. In mice, this ability is acquired during thymic development. We explored the transcriptional landscape of Tinncompared to conventional T cells (Tconv) in the human thymus and blood using single cell RNA sequencing and flow cytometry. We reveal that in human blood, the majority of Tinncells, including iNKT, MAIT, and Vδ2+Vγ9+T cells, share an effector program characterized by the expression of unique chemokine and cytokine receptors, and cytotoxic molecules. This program is driven by specific transcription factors, distinct from those governing Tconvcells. Conversely, only a fraction of thymic Tinncells displays an effector phenotype, while others share transcriptional features with developing Tconvcells, indicating potential divergent developmental pathways. Unlike the mouse, human Tinncells do not differentiate into multiple effector subsets but develop a mixed type I/type III effector potential. To conduct a comprehensive cross-species analysis, we constructed a murine Tinndevelopmental atlas and uncovered additional species-specific distinctions, including the absence of type II Tinncells in humans, which implies distinct immune regulatory mechanisms across species. The study provides insights into the development and functionality of Tinncells, emphasizing their role in immune responses and their potential as targets for therapeutic interventions.

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Section: Gene Expressionsupporting

confidence: 90%

Unraveling the Phenotypic States of Human innate-like T Cells: Comparative Insights with Conventional T Cells and Mouse Models

Loh,

Carcy,

Krovi

et al. 2023

Preprint

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“…Immunohistochemical results of AIH liver specimens confirm a significant accumulation of IL‐26 spatially distributed in liver portal areas and lesions of interface hepatitis. Studies have revealed the multiple cellular sources of IL‐26, including T cells, natural killer (NK) cells, NKp30 + γδT cells, CD68 + macrophages and, more recently, lung mucosal‐associated invariant T (MAIT) cells 31,33,34 . In our study, in situ confocal staining speculated that CD4 + T cells, CD8 + T cells and CD68 + macrophages in AIH represent hepatic reservoirs of IL‐26.…”

Section: Discussionmentioning

confidence: 71%

“…Studies have revealed the multiple cellular sources of IL-26, including T cells, natural killer (NK) cells, NKp30 + γδT cells, CD68 + macrophages and, more recently, lung mucosalassociated invariant T (MAIT) cells. 31,33,34 Th cell subsets. 10 Increased circulating soluble PD-1 levels, alongside with the frequency of PD-1 + CD8 + T cells, are positively associated with liver pathological markers in AIH.…”

Section: Discussionmentioning

confidence: 99%

IL‐26 modulates T cell function in autoimmune hepatitis

Qian

Liu

et al. 2023

J of Digest Diseases

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Objectives: Autoimmune hepatitis (AIH) is an aberrant autoimmune condition mediated by T cell abnormality, which may cause fulminant liver failure and persistent liver injury. This study aimed to disclose the histopathological and functional engagement of interleukin (IL)-26, a potent inflammation mediator, in AIH disease progression. Methods: We conducted immunohistochemical staining on liver biopsy samples to evaluate intrahepatic expression of IL-26. Cellular sources of hepatic IL-26 were detected by confocal microscopy. Flow cytometry was employed to determine the immunological alterations of CD4 + and CD8 + T cells following in vitro IL-26 treatment on primary peripheral blood mononuclear cells from healthy controls. Results: Statistically significant increase in IL-26 level was observed in AIH (n = 48) liver samples in comparison with patients having chronic hepatitis B (n = 25), nonalcoholic fatty liver disease (n = 18), and healthy donors for living donor liver transplantation (n = 10). The number of intrahepatic IL-26 + cells was positively correlated with histological and serological severity. An immunofluorescence staining indicated that liver-infiltrating CD4 + T cells, CD8 + T cells, and CD68 + macrophages orchestrated IL-26 secretion in AIH. Both CD4 + and CD8 + T cells demonstrated effective activation, lytic, and proinflammatory functions upon IL-26 stimulation. Conclusion: We observed elevated IL-26 in AIH liver which promoted T cell activation and cytotoxic capacity, indicating a therapeutic potential of IL-26 intervention in AIH.

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“…The high levels of Th1 and Th2 cytokines secretion also indicated that cellular immunity was activated, clearing pathogenic bacteria and protecting organs from infection. IL-12 has been shown to promote cytotoxicity of pulmonary mucosal-associated invariant T cells and improve clearance of pathogenic bacteria by mucosal immunity ( 57 ). Overall, high survival rates are generally associated with better tissue protection.…”

Section: Discussionmentioning

confidence: 99%

Comparative study of subcutaneous, intramuscular, and oral administration of bovine pathogenic Escherichia coli bacterial ghost vaccine in mice

Lei

Zheng

et al. 2022

Front. Immunol.

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Escherichia coli is one of the most common bacterial pathogens in cattle. Prophylactic vaccines are considered promising strategies with the potential to reduce the incidence of colibacillosis. Some studies suggested that bacterial ghosts may serve as a novel approach for preventing bacterial infections. However, the roles of administration route on vaccine immunogenicity and efficacy have not been investigated. In this study, the efficacy of vaccination via different immune routes in generating humoral and cellular immune response was compared through subcutaneous (SC), intramuscular (IM), and oral (O) administration in female BALB/c mice with bacterial ghosts prepared using wild type Escherichia coli isolates CE9, while phosphate buffer saline (PBS) and inactivated vaccines containing aluminum adjuvants (Killed) were used as control. Our results showed that the plasmid pBV220-E-aa-SNA containing E. coli was efficiently cleaved at 42°C with 94.8% positive ratio as assessed by colony counts. Transmission electron microscopy (TEM) confirmed bacteria retained intact surface structure while devoid of cytoplasmic component. We found that total IgG titers in killed, IM and SC groups showed significant increase on 7, 14, 21 and 28 days post-immunization. The IgA level of the IM group was higher than that of all other groups on the 28th day. Meanwhile, four experimental groups showed a significant difference in IgA levels compared with PBS control. In the IM group, an increase in the relative percentages of CD3+CD4+ T cells was accompanied by an increase in the relative percentages of splenic CD3+CD8+ T cells. In comparison with the inactivated vaccine, intramuscular CE9 ghosts immunization elicited higher levels of IL-1β, IL-2, IL-6 and IL-12. Subcutaneous and intramuscular immunizations were significantly associated with improved survival in comparison with oral route, traditional vaccine and the control. Pathologic assessment revealed that less severe tissue damage and inflammation were found in lung, kidney, and intestine of IM group compared with other groups. The results above demonstrate that immunization of Escherichia coli CE9 ghosts via intramuscular injection elicits a more robust antigen-specific immune response in mice to prevent the Escherichia coli infection.

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Human lung-resident mucosal-associated invariant T cells are abundant, express antimicrobial proteins, and are cytokine responsive

Cited by 21 publications

References 58 publications

Unraveling the Phenotypic States of Human innate-like T Cells: Comparative Insights with Conventional T Cells and Mouse Models

Unraveling the Phenotypic States of Human innate-like T Cells: Comparative Insights with Conventional T Cells and Mouse Models

IL‐26 modulates T cell function in autoimmune hepatitis

Comparative study of subcutaneous, intramuscular, and oral administration of bovine pathogenic Escherichia coli bacterial ghost vaccine in mice

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