Effector γδ T Cell Differentiation Relies on Master but Not Auxiliary Th Cell Transcription Factors

Barros‐Martins, Joana; Schmolka, Nina; Fontinha, Diana; Miranda, Marta Pires de; Simas, J. Pedro; Brok, Ingrid C.; Ferreira, Cristina; Veldhoen, Marc; Silva‐Santos, Bruno; Serre, Karine

doi:10.4049/jimmunol.1501921

Cited by 67 publications

(71 citation statements)

References 71 publications

(109 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whether CCR6 repression in Th17 cells occurs to disrupt barrier tissue-homing and promote recruitment to inflamed tissue, as we show in γδT17 cells, is unclear. Despite γδT17 cell development occurring independently of IRF4 and BATF4950, we report that these factors suppress Ccr6 expression in γδT17 cells upon IL-23- and IL-1β-driven activation. This is likely to be cooperative, as has been shown during Th17 cell development43.…”

Section: Discussionmentioning

confidence: 56%

IL-17-producing γδ T cells switch migratory patterns between resting and activated states

et al. 2017

View full text Add to dashboard Cite

Interleukin 17-producing γδ T (γδT17) cells have unconventional trafficking characteristics, residing in mucocutaneous tissues but also homing into inflamed tissues via circulation. Despite being fundamental to γδT17-driven early protective immunity and exacerbation of autoimmunity and cancer, migratory cues controlling γδT17 cell positioning in barrier tissues and recruitment to inflammatory sites are still unclear. Here we show that γδT17 cells constitutively express chemokine receptors CCR6 and CCR2. While CCR6 recruits resting γδT17 cells to the dermis, CCR2 drives rapid γδT17 cell recruitment to inflamed tissues during autoimmunity, cancer and infection. Downregulation of CCR6 by IRF4 and BATF upon γδT17 activation is required for optimal recruitment of γδT17 cells to inflamed tissue by preventing their sequestration into uninflamed dermis. These findings establish a lymphocyte trafficking model whereby a hierarchy of homing signals is prioritized by dynamic receptor expression to drive both tissue surveillance and rapid recruitment of γδT17 cells to inflammatory lesions.

show abstract

Section: Discussionmentioning

confidence: 56%

IL-17-producing γδ T cells switch migratory patterns between resting and activated states

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Because the transcriptional profiles of Th17 cells and gdT17 cells are similar in many aspects (28,29), we investigated whether IL-2 was a relevant determinant of thymic gdT17 development. Thymic IL-2 expression decreases before birth and resumes postnatally (Supplemental Fig.…”

Section: Resultsmentioning

confidence: 99%

“…None of the auxilliary transcription factors of the Th17 profile, which have recently been described to be dispensable for the development of gdT17 cells (29), were regulated (Fig. 7A).…”

Section: Engagement Of the Gd Tcr Contributes To The Commitment Of Gdmentioning

confidence: 91%

IL-1β and IL-23 Promote Extrathymic Commitment of CD27+CD122− γδ T Cells to γδT17 Cells

Muschaweckh

Petermann

Korn

2017

The Journal of Immunology

View full text Add to dashboard Cite

γδT17 cells are a subset of γδ T cells committed to IL-17 production and are characterized by the expression of IL-23R and CCR6 and lack of CD27 expression. γδT17 cells are believed to arise within a narrow time window during prenatal thymic development. In agreement with this concept, we show in this study that adult Rag1−/− recipient mice of Il23rgfp/+ (IL-23R reporter) bone marrow selectively lack IL-23R+ γδT17 cells. Despite their absence in secondary lymphoid tissues during homeostasis, γδT17 cells emerge in bone marrow chimeric mice upon induction of skin inflammation by topical treatment with imiquimod cream (Aldara). We demonstrate that IL-1β and IL-23 together are able to promote the development of bona fide γδT17 cells from peripheral CD122−IL-23R− γδ T cells, whereas CD122+ γδ T cells fail to convert into γδT17 cells and remain stable IFN-γ producers (γδT1 cells). IL-23 is instrumental in expanding extrathymically generated γδT17 cells. In particular, TCR-Vγ4+ chain–expressing CD122−IL-23R− γδ T cells are induced to express IL-23R and IL-17 outside the thymus during skin inflammation. In contrast, TCR-Vγ1+ γδ T cells largely resist this process because prior TCR engagement in the thymus has initiated their commitment to the γδT1 lineage. In summary, our data reveal that the peripheral pool of γδ T cells retains a considerable degree of plasticity because it harbors “naive” precursors, which can be induced to produce IL-17 and replenish peripheral niches that are usually occupied by thymus-derived γδT17 cells.

show abstract

“…A previous report suggested that T-bet and RORγt promote the differentiation of T cells into Th1/Tc1 and Th17/Tc17 subsets, respectively [47]. Recently, it has become clear that both Th1 and Th17 cytokines are key players in the development of RA [48]. Furthermore, we observed that Sema7A significantly enhanced the production of Th17/Tc17 cytokines, including IFN-γ, IL-22, and IL-17, in comparison with cells treated with DSema7A.…”

Section: Discussionmentioning

confidence: 99%

Semaphorin 7A as a potential immune regulator and promising therapeutic target in rheumatoid arthritis

Xie

Wang

2017

Arthritis Res Ther

View full text Add to dashboard Cite

BackgroundSemaphorin 7A (Sema7A) is expressed by several different classes of lymphoid and myeloid cells and is a potent immunomodulator. We examined the role of Sema7A in modulating cellular immune responses and to provide experimental data validating the therapeutic potential of Sema7A in rheumatoid arthritis (RA).MethodsSoluble Sema7A (sSema7A) levels in the serum and synovial fluid from patients with RA or osteoarthritis, as well as cytokine secretions, were analyzed with an enzyme-linked immunosorbent assay. The cell surface levels and transcripts of Sema7A were evaluated in T cells and monocytes from patients with RA. The effect of Sema7A on the functions of primary T cells isolated from the peripheral blood of healthy donors was observed. Detection of the activation of the signal mediator focal adhesion kinase was performed by Western blotting. Shedding of sSema7A was evaluated in monocytes. The introduction of anti-Sema7A antibody to mice with collagen-induced arthritis (CIA) was observed in vivo.ResultsUpregulation of sSema7A levels in both the serum and synovial fluid of patients with RA was correlated with disease activity markers. sSema7A markedly increased Th1/Th17 cytokine secretion and induced evident upregulation of T-bet and retinoic acid receptor-related orphan nuclear receptor γt levels in T cells. Cell surface Sema7A was cleaved by a disintegrin and metalloprotease 17 (ADAM17) in monocytes. Interleukin-6 and tumor necrosis factor-α stimulated ADAM17 secretion in synovial macrophages. Blocking of β1-integrin abrogated the Sema7A-mediated cytokine secretion. Treatment with an anti-Sema7A antibody significantly attenuated CIA.ConclusionsThese findings indicate that Sema7A as a potent activator of T cells and monocytes in the immune response contributes to the inflammation and progression of RA, suggesting its therapeutic potential in the treatment of RA.

show abstract

Effector γδ T Cell Differentiation Relies on Master but Not Auxiliary Th Cell Transcription Factors

Cited by 67 publications

References 71 publications

IL-17-producing γδ T cells switch migratory patterns between resting and activated states

IL-17-producing γδ T cells switch migratory patterns between resting and activated states

IL-1β and IL-23 Promote Extrathymic Commitment of CD27+CD122− γδ T Cells to γδT17 Cells

Semaphorin 7A as a potential immune regulator and promising therapeutic target in rheumatoid arthritis

Contact Info

Product

Resources

About