Activated Murine B Lymphocytes and Dendritic Cells Produce a Novel CC Chemokine which Acts Selectively on Activated T Cells

Schaniel, Christoph; Pardali, Evangelia; Sallusto, Federica; Speletas, Matthaios; Ruedl, Christiane; Shimizu, Takeyuki; Seidl, Thomas; Andersson, Jan; Melchers, Fritz; Rolink, Antonius; Sideras, Paschalis

doi:10.1084/jem.188.3.451

Cited by 146 publications

(139 citation statements)

References 74 publications

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“…Total RNA was extracted from snapfrozen submandibular glands, using RNAzol B (Invitrogen, Carlsbad, CA). The following specific primers for murine chemokines and cytokines were used: for IP-10 (13) forward 5Ј-GGAAGCCTCCCCATCAGCACC-3Ј, reverse 5Ј-AGA-CAGGCTCTCTGCTGTCCA-3Ј; for Mig (17) forward 5Ј-GAGGAACCCTAGTGATAAGGA-3Ј, reverse 5Ј-CCTT-GAACGACGACGACTTTG-3Ј; for I-TAC (18) forward 5Ј-CTTCCTTATGTTCAAACAGGG-3Ј, reverse 5Ј-ACGT-TCCCAGGATGTCACATG-3Ј; for TARC (19) forward 5Ј-AGCTGCTCGAGCCACCAATGT-3Ј, reverse 5Ј-TCA-GCGGGAAGGTCATGGCCT-3Ј; for MDC (20) forward 5Ј-TCCCACTCCTGGTGGCTCTCG-3Ј, reverse 5Ј-CATGGT-CATCAGGTCCTCCTC-3Ј; for interleukin-2 receptor (IL-2R) (21) forward 5Ј-CTCTCATTAACCATAGTACCC-3Ј, reverse 5Ј-TGCTCTTTCTGGTGTTCAAGT-3Ј; for IFN␥ (10) forward 5Ј-CACGGCACAGTCATTGAAAGCC-3Ј, reverse 5Ј-CTTATTGGGACAATCTCTTCCC-3Ј; for IL-4 (22) forward 5Ј-TTGTCTCTCGTCACTGACGGC-3Ј, reverse 5Ј-CATGGTGGCTCAGTACTACGA-3Ј; and for GAPDH (10) forward 5Ј-GGTGGAGGTCGGAGTCAACG-3Ј, reverse 5Ј-CAAAGTTGTCATGGATGACC-3Ј. The required fragments were amplified by RT-PCR using an RNA PCR kit (Takara Shuzo).…”

Section: Methodsmentioning

confidence: 99%

Antagonist of interferon‐inducible protein 10/CXCL10 ameliorates the progression of autoimmune sialadenitis in MRL/lpr mice

Hasegawa¹,

Inoue²,

Kohno³

et al. 2006

Arthritis & Rheumatism

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Objective. Mononuclear cell infiltration of the salivary glands is a major feature of Sjögren's syndrome (SS) and its animal model. Local generation of chemokines and the presence of chemokine receptors on the infiltrating cells may be involved in this process. We undertook the present study to investigate the expression of chemokines during the development of autoimmune sialadenitis in MRL/lpr mice and the therapeutic effect of chemokine antagonists on sialadenitis.Methods. NH 2 -terminal-truncated interferoninducible protein 10 (IP-10)/CXCL10 analogs were transfected into a nonmetastatic fibroblastoid cell line, MRL/N-1, and injected subcutaneously into MRL/lpr mice, and the effects on sialadenitis were monitored.Results. IP-10 analogs truncated by 5 or more amino acid residues from the N-terminal failed to induce chemotaxis and calcium influx by CXCR3-expressing cells. Of these, the most potent antagonist (AT) (IP-10-AT) was a molecule with methionine added after removal of the 5 N-terminal amino acid residues. Significantly increased expression of the Th1-associated chemokines IP-10, monokine induced by interferon-␥/ CXCL9, and interferon-inducible T cell chemoattractant/CXCL11 was induced in the ductal epithelium by interferon-␥ produced in the salivary glands, whereas expression of the Th2-associated chemokines thymus and activation-regulated chemokine (TARC)/ CCL17 and monocyte-derived chemokine/CCL22 was almost undetectable during sialadenitis. Inoculation of IP-10-AT into MRL/lpr mice during the early stage of sialadenitis significantly reduced periductal mononuclear cell infiltration and parenchymal destruction compared with these features in control and TARC-ATbearing mice. This was due to a significant reduction in infiltration of CXCR3؉ T cells, predominantly Th1 cells, resulting in decreased interferon-␥ production.Conclusion. We prepared a novel potent IP-10 antagonist and demonstrated its ability to ameliorate the progression of autoimmune sialadenitis. This agent may provide a new therapeutic approach to SS.

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Section: Methodsmentioning

confidence: 99%

Antagonist of interferon‐inducible protein 10/CXCL10 ameliorates the progression of autoimmune sialadenitis in MRL/lpr mice

Hasegawa¹,

Inoue²,

Kohno³

et al. 2006

Arthritis & Rheumatism

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“…53 In addition, CCR4 is expressed selectively on Th2 cells; however, Th1 and Th2 cells are attracted by MDC. 31 Furthermore, it has been reported that truncated MDC (3-69) has reduced chemotactic activity for lymphocytes, but not for monocytes. 54 Degenerated oligonucleotide-based RT-PCR was used to identify candidate MDC receptors in nephritic glomeruli.…”

Section: Discussionmentioning

confidence: 99%

Mononuclear Cell-Infiltrate Inhibition by Blocking Macrophage-Derived Chemokine Results in Attenuation of Developing Crescentic Glomerulonephritis

García

Xia

Harrison

et al. 2003

The American Journal of Pathology

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“…However, the human and murine homologues of MDC and TARC are relatively conserved between species. Human and murine homologues of MDC bear 75% sequence identity at the nucleotide level (47,48), whereas human and murine homologues of TARC bear 72% nucleotide sequence identity (49,50). A panel of anti-human CCR4 monoclonal antibodies was characterized with respect to functional antagonism of gpCCR4 using in vitro assays of chemotactic responsiveness.…”

Section: Discussionmentioning

confidence: 99%

The Identification, Characterization, and Distribution of Guinea Pig CCR4 and Epitope Mapping of a Blocking Antibody

Jopling¹,

Sabroe²,

Andrew³

et al. 2002

Journal of Biological Chemistry

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Th2 lymphocytes play a central role in the control and maintenance of allergic inflammation. The chemokine receptor CCR4 is preferentially expressed on the surface of Th2 lymphocytes polarised in vitro. However, CCR4 is found on the surface of a significant proportion of circulating memory T lymphocytes, some of which are capable of producing the Th1-associated cytokine interferon ␥. To investigate the function of CCR4 on guinea pig (gp) T lymphocytes, we identified the open-reading frame of gpCCR4, which encodes a 361-amino acid protein with 88 and 81% amino acid identity to human and murine CCR4 sequences, respectively. Cells transfected with gpCCR4 migrated toward the human and murine orthologues of the CCR4 ligands, macrophage-derived chemokine and thymus and activation-regulated chemokine. Surface expression of CCR4, using an anti-human CCR4 monoclonal antibody, 10E4, was detected on ϳ12% of guinea pig peripheral blood T helper cells, and CCR4 ؉ guinea pig thymocytes were detected in low numbers. However, CCR4؉ T helper cells constituted ϳ9% of the T lymphocyte population within the normal guinea pig lung and 52% of the guinea pig bronchoalveolar lavage fluid, which is consistent with a role for CCR4 in T lymphocyte development and trafficking through normal tissues. Subsequent analysis of chimeric chemokine receptors indicated that 10E4, a functional inhibitor of gpCCR4 responses, recognized the amino terminus of CCR4.Allergic inflammation of the lung in diseases such as asthma is largely controlled and maintained by the recruitment of antigen-specific T lymphocytes to the lung tissue (1). The Th2-type lymphocytes that predominate at sites of allergic inflammation secrete cytokines such as IL-4, IL-5 and IL-13, 1 which influence the actions of other leukocyte populations involved in the inflammatory response (2, 3). For example, IL-4 and IL-13 can induce B lymphocyte production of IgE (4, 5) and airway epithelial cell generation of eotaxin, which is central to eosinophil recruitment (6, 7), whereas IL-5 is a potent eosinophil maturation and survival factor (8, 9). Overexpression of IL-13 in the lung causes many of the histopathological and physiological features of asthma (10). Increasing evidence suggests that chemokines are important regulators of the selective trafficking of leukocytes in homeostasis, hematopoiesis, and inflammation (11). Chemokines can be divided into four subfamilies dependent upon the position of their amino-terminal cysteine residues; the two main chemokine groups are the CXCL and the CCL subfamilies (12), which signal via CXCR and CCR receptors belonging to the G-protein coupled receptor superfamily (13,14). The differential expression of chemokine receptors on the surface of leukocytes contributes to the selective recruitment of cells to specific sites, and, consequently, these receptors may provide useful targets for therapeutic intervention in the modulation of inflammatory disorders. Studies of T lymphocytes polarized in vitro have shown that Th1 cells preferentially express CC...

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Activated Murine B Lymphocytes and Dendritic Cells Produce a Novel CC Chemokine which Acts Selectively on Activated T Cells

Cited by 146 publications

References 74 publications

Antagonist of interferon‐inducible protein 10/CXCL10 ameliorates the progression of autoimmune sialadenitis in MRL/lpr mice

Antagonist of interferon‐inducible protein 10/CXCL10 ameliorates the progression of autoimmune sialadenitis in MRL/lpr mice

Mononuclear Cell-Infiltrate Inhibition by Blocking Macrophage-Derived Chemokine Results in Attenuation of Developing Crescentic Glomerulonephritis

The Identification, Characterization, and Distribution of Guinea Pig CCR4 and Epitope Mapping of a Blocking Antibody

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