Correction: LFA-1/ICAM-1 Ligation in Human T Cells Promotes Th1 Polarization through a GSK3β Signaling–Dependent Notch Pathway

Verma, Navin Kumar; Fazil, M. H. U. Turabe; Ong, Seow Theng; Chalasani, Madhavi Latha Somaraju; Low, Jian Hui; Kottaiswamy, Amuthavalli; Praseetha, P; Kizhakeyil, Atish; Kumar, Sunil; Panda, Aditya K.; Freeley, Michael; Smith, Sinead; Boehm, Bernhard O.; Kelleher, Dermot

doi:10.4049/jimmunol.1601160

Cited by 7 publications

(5 citation statements)

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“…Verma et al and others demonstrated that LFA-1 signaling promoted Th1 differentiation by upregulating T-bet expression. [45][46][47][48] This result would explain the high expression of T-bet in naive T cells cultured with IFNγ-pretreated KCs in the presence of CD58/CD2 blockade ( Figure S5C). In addition, another study showed that the interaction of CD54/LFA-1 increased the phosphorylation of STAT3 and inhibited differentiation into Th2 cells.…”

Section: Discussionmentioning

confidence: 91%

Keratinocytes costimulate naive human T cells via CD2: a potential target to prevent the development of proinflammatory Th1 cells in the skin

et al. 2019

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The interplay between keratinocytes and immune cells, especially T cells, plays an important role in the pathogenesis of chronic inflammatory skin diseases. During psoriasis, keratinocytes attract T cells by releasing chemokines, while skin-infiltrating selfreactive T cells secrete proinflammatory cytokines, e.g., IFNγ and IL-17A, that cause epidermal hyperplasia. Similarly, in chronic graftversus-host disease, allogenic IFNγ-producing Th1/Tc1 and IL-17-producing Th17/Tc17 cells are recruited by keratinocyte-derived chemokines and accumulate in the skin. However, whether keratinocytes act as nonprofessional antigen-presenting cells to directly activate naive human T cells in the epidermis remains unknown. Here, we demonstrate that under proinflammatory conditions, primary human keratinocytes indeed activate naive human T cells. This activation required cell contact and costimulatory signaling via CD58/CD2 and CD54/LFA-1. Naive T cells costimulated by keratinocytes selectively differentiated into Th1 and Th17 cells. In particular, keratinocyte-initiated Th1 differentiation was dependent on costimulation through CD58/CD2. The latter molecule initiated STAT1 signaling and IFNγ production in T cells. Costimulation of T cells by keratinocytes resulting in Th1 and Th17 differentiation represents a new explanation for the local enrichment of Th1 and Th17 cells in the skin of patients with a chronic inflammatory skin disease. Consequently, local interference with T cell-keratinocyte interactions may represent a novel strategy for the treatment of Th1 and Th17 cell-driven skin diseases.In addition, in chronic graft-versus-host disease (GVHD), a major complication of allogenic stem cell transplantation, the KCmediated secretion of chemokines (CXCL9 and CXCL10) leads to the recruitment of alloreactive T cells into the skin. 14 These allogenic T cells predominantly belong to the IFNγ-producing Th1/ Tc1 and IL-17-producing Th17/Tc17 subpopulations and cause cutaneous manifestations, e.g., follicular erythema. [15][16][17] Although the pivotal role of KCs in non-contact-mediated communication during chronic skin inflammation is quite well understood, the direct interaction between KCs and T cells remains elusive. In particular, the potential of KCs to act as nonprofessional APCs, enabling them to costimulate T cells directly in the skin, is still debated.T cells require two distinct signals for activation and clonal expansion. The first signal is transmitted by the antigen-specific T cell receptor (TCR) on T cells, following recognition of antigenic peptides loaded on MHC class I or class II molecules expressed by APCs. The first signal secures the antigen specificity of the immune reaction. The second signal is transmitted through costimulatory receptors, dictating the progression to T cell activation. Between

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Section: Discussionmentioning

confidence: 91%

Keratinocytes costimulate naive human T cells via CD2: a potential target to prevent the development of proinflammatory Th1 cells in the skin

et al. 2019

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“…To test the potential impact of miR-31 function on the rearrangement of the actin cytoskeleton, we assessed the adhesion of Th1 rep cells restimulated with PMA/ionomycin in the presence of CXC motif chemokine (CXCL) 10 and Intracellular Adhesion Molecule 1 (ICAM-1), i.e., the respective ligands for CXCR3 and Lymphocyte function-associated antigen 1 (LFA-1), both of which are expressed on Th1 rep cells (44, 45). We observed an increase of ~40% in adherent Th1 rep cell number after inhibition of miR-31.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA-31 Reduces the Motility of Proinflammatory T Helper 1 Lymphocytes

et al. 2018

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Proinflammatory type 1 T helper (Th1) cells are enriched in inflamed tissues and contribute to the maintenance of chronic inflammation in rheumatic diseases. Here we show that the microRNA- (miR-) 31 is upregulated in murine Th1 cells with a history of repeated reactivation and in memory Th cells isolated from the synovial fluid of patients with rheumatic joint disease. Knock-down of miR-31 resulted in the upregulation of genes associated with cytoskeletal rearrangement and motility and induced the expression of target genes involved in T cell activation, chemokine receptor– and integrin-signaling. Accordingly, inhibition of miR-31 resulted in increased migratory activity of repeatedly activated Th1 cells. The transcription factors T-bet and FOXO1 act as positive and negative regulators of T cell receptor (TCR)–mediated miR-31 expression, respectively. Taken together, our data show that a gene regulatory network involving miR-31, T-bet, and FOXO1 controls the migratory behavior of proinflammatory Th1 cells.

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“…For example, LFA-1 activates GSK-3b and the g-secretase complex, which subsequently cleaves Notch-1 from the human CD4 + T cell surface [70]. The released intracellular signaling domain of Notch-1 (NICD) translocates to the nucleus and mediates the expression of the Notch-1 target genes, HEY1 and HES1.…”

Section: Lfa-1 Further Enforces the Th1 Program By Concurrently Inhib...mentioning

confidence: 99%

LFA-1 in T cell priming, differentiation, and effector functions

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Kemper

et al. 2021

Trends in Immunology

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Correction: LFA-1/ICAM-1 Ligation in Human T Cells Promotes Th1 Polarization through a GSK3β Signaling–Dependent Notch Pathway

Cited by 7 publications

References 0 publications

Keratinocytes costimulate naive human T cells via CD2: a potential target to prevent the development of proinflammatory Th1 cells in the skin

Keratinocytes costimulate naive human T cells via CD2: a potential target to prevent the development of proinflammatory Th1 cells in the skin

MicroRNA-31 Reduces the Motility of Proinflammatory T Helper 1 Lymphocytes

LFA-1 in T cell priming, differentiation, and effector functions

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