Differential Expression of Chemokine Receptors and Chemotactic Responsiveness of Type 1 T Helper Cells (Th1s) and Th2s

Bonecchi, Raffaella; Bianchi, Giancarlo; Panina-Bordignon, Paola; D’Ambrosio, Daniele; Lang, Rosmarie; Borsatti, Alessandro; Sozzani, Silvano; Allavena, Paola; Gray, Patrick A.; Mantovani, Alberto; Sinigaglia, Francesco

doi:10.1084/jem.187.1.129

Cited by 1,905 publications

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“…Chemokines mediate local inflammatory responses by their ability to recruit T cells and other cells of the immune system, providing that these cells express certain chemokine receptors [38]. Several chemokine receptors have been associated with recruitment of T H 1 T cells to sites of inflammation [39]. The contribution of CCR5 to the pathogenesis of autoimmune diabetes in NOD mice was indirectly demonstrated by reduced insulitis and protection from diabetes in NOD.…”

Section: Discussionmentioning

confidence: 99%

Homing of human autoreactive T cells into pancreatic tissue of NOD-scid mice

Halteren¹,

Kardol²,

Mulder³

et al. 2004

Diabetologia

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Aims/hypothesis: An important prerequisite for the initiation of pancreatic islet inflammation is the recruitment of pathogenic T cells. We investigated the in vivo migration patterns of human islet-reactive T cell clones after transfer into compromised hosts. Methods: NOD-scid mice were injected with a mixture of human autoreactive T cells and antigen-presenting cells. Survival and migration of T cells was analysed by fluorescenceactivated cell sorter and immunohistochemical analysis of various tissues.

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Section: Discussionmentioning

confidence: 99%

Homing of human autoreactive T cells into pancreatic tissue of NOD-scid mice

Halteren¹,

Kardol²,

Mulder³

et al. 2004

Diabetologia

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“…In EM (CD45RA À CCR7 À ) Th cells [30], Hopx expression was up-regulated 18-fold, as compared with naïve Th cells. In ''terminally differentiated'' EM (CD45RA À CCR7 À CD27 À ) Th cells [31,32], Hopx was up-regulated 38-fold, and 45-fold in EM (CD45RA À CCR7 À CCR5 1 ) Th1 cells [33], again in comparison to naïve Th cells. In regulatory (CD25 hi CD127 À ) Th cells [34] and in Th2 EM (CD45RA À CCR7 À CRTh2 1 ) (CRTh2, chemoattractant receptor-homologous molecule expressed on Th2 cells) cells [35] (Fig.…”

Section: Hopx Expression Is Induced By T-betmentioning

confidence: 94%

Persistence of effector memory Th1 cells is regulated by Hopx

et al. 2010

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Th1 cells are prominent in inflamed tissue, survive conventional immunosuppression, and are believed to play a pivotal role in driving chronic inflammation. Here, we identify homeobox only protein (Hopx) as a critical and selective regulator of the survival of Th1 effector/memory cells, both in vitro and in vivo. Expression of Hopx is induced by T-bet and increases upon repeated antigenic restimulation of Th1 cells. Accordingly, the expression of Hopx is low in peripheral, naïve Th cells, but highly up-regulated in terminally differentiated effector/memory Th1 cells of healthy human donors. In murine Th1 cells, Hopx regulates the expression of genes involved in regulation of apoptosis and survival and makes them refractory to Fas-induced apoptosis. In vivo, adoptively transferred Hopxdeficient murine Th1 cells do not persist. Consequently, they cannot induce chronic inflammation in murine models of transfer-induced colitis and arthritis, demonstrating a key role of Hopx for Th1-mediated immunopathology.Key words: Cell survival . CD4 T cells . Inflammation . Memory cells Supporting Information available onlineIntroduction T-helper type 1 (Th1) cells mediate immune responses to intracellular pathogens, such as viruses, and produce IFN-g as their signature cytokine [1]. IFN-g, together with IL-12 and the transcription factors STAT1, STAT4 and T-bet, promotes the development of Th1 cells [2][3]. T-bet (T-box 21) is considered to act as the master transcription factor critically regulating Th1 lineage commitment [3][4][5]. Apart from their protective role in clearing infections, Th1 cells can initiate and maintain chronic inflammatory diseases, e.g. inflammatory bowel disease [6][7][8][9], uveitis [10], EAE [11,12] and arthritis [13]. In vitro, Th1 cells are much more sensitive to Fas-mediated apoptosis than Th2 or Th17 cells [14][15][16][17][18][19][20]. In vivo, however, effector/memory Th1 cells are abundant in chronically inflamed tissue [21][22][23] and persist over long time periods [24][25][26], suggesting that their sensitivity to Eur. J. Immunol. 2010. 40: 2993-3006 DOI 10.1002 HIGHLIGHTS 2993 FrontlineFas-mediated apoptosis is strictly regulated. Here, we demonstrate that among CD4 1 T cells, the transcriptional cofactor homeobox only protein (Hopx) is expressed by repeatedly restimulated Th1 cells, but not by Th2, Th17 or regulatory T cells. Hopx regulates Fas-mediated apoptosis of effector/memory Th1 cells and is critically required for their persistence in vivo.In vertebrates, Hopx expression originally was detected in the myocardium [27,28]. There, expression of Hopx is induced by the cardiac transcription factor Nkx2-5. Hopx-deficient mice show a complex, incompletely penetrant phenotype. Some Hopxdeficient embryos have a poorly developed myocardium with reduced cell numbers, others show normal, and still others show increased numbers of cardiomyocytes after birth [27,28]. Hopx does not bind to homeobox consensus binding sequences, and it has been postulated that Hopx acts indirectly, partnering with ...

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“…Binding of ligand to CXCR3 is crucial for chemotaxis of these receptor positive cells to inflammatory sites (5). CXCL10 is regarded as a chemoattractant preferentially for activated T-cells (6) and particularly Th1 cells (7).…”

Section: Macrophages Dendritic Cells and Natural Killer T-cells) Andmentioning

confidence: 99%

Enhanced Expression of CXCL10 in Inflammatory Bowel Disease

Østvik

Granlund

Bugge

et al. 2013

Inflammatory Bowel Diseases

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We explored the gene expression in colonic biopsies of active and inactive inflammatory bowel disease (IBD), in an extensive material of ulcerative colitis (UC) and Crohn`s disease (CD). The chemokine CXCL10 and its receptor CXCR3 were among the upregulated genes.This study examines the expression of CXCL10 and the mechanisms for its release in patients with UC or CD, and in intestinal epithelial cell (IEC) lines. Methods

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Differential Expression of Chemokine Receptors and Chemotactic Responsiveness of Type 1 T Helper Cells (Th1s) and Th2s

Cited by 1,905 publications

References 40 publications

Homing of human autoreactive T cells into pancreatic tissue of NOD-scid mice

Homing of human autoreactive T cells into pancreatic tissue of NOD-scid mice

Persistence of effector memory Th1 cells is regulated by Hopx

Enhanced Expression of CXCL10 in Inflammatory Bowel Disease

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