IL-10 inhibits CD28 and ICOS costimulations of T cells via src homology 2 domain—containing protein tyrosine phosphatase 1

Taylor, Alison; Akdiş, Mübeccel; Joss, Andrea; Akkoç, Tunç; Wenig, Renate; Colonna, Marco; Daigle, Isabelle; Flory, Egbert; Blaser, Kurt

doi:10.1016/j.jaci.2007.04.004

Cited by 104 publications

(94 citation statements)

References 35 publications

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“…Similarly, the SH2-domain-containing protein tyrosine phosphatase 1 (SHP-1) can reduce costimulation as observed in SHP-1-deficient CD4 + thymocytes. 106,107 In keeping with this, SHP-1 associates in a complex with Vav1, Grb-2 and Sos1. 105 The suppressor cytokine IL-10 has also been reported to activate SHP-1 and in the process, suppress PI3K binding to CD28.…”

Section: Cd28 and Negative Regulationmentioning

confidence: 67%

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CD28 co‐signaling in the adaptive immune response

Riha¹,

Rudd²

2010

Self/Nonself

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Section: Cd28 and Negative Regulationmentioning

confidence: 67%

“…105 The suppressor cytokine IL-10 has also been reported to activate SHP-1 and in the process, suppress PI3K binding to CD28. 106,108 Phosphatases such as SHIP 109 and SHP-2, 110 have also been implicated in CD28 co-signaling, although the molecular basis remains to be elucidated.…”

Section: Cd28 and Negative Regulationmentioning

confidence: 99%

CD28 co‐signaling in the adaptive immune response

Riha¹,

Rudd²

2010

Self/Nonself

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“…IL-10 can also inhibit the release of IFN-γ and IL-2 and thus inhibit T cell growth [50]. This immunosuppressive effect of IL-10 is mediated by blocking the CD28 and ICOS costimulatory signaling [51,52].…”

Section: Immunosuppressive and Tolerogenic Activity Of Regulatory Denmentioning

confidence: 99%

Immunosuppressive Mechanisms of Regulatory Dendritic Cells in Cancer

Shurin

2013

Cancer Microenvironment

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Three major functional subsets of dendritic cells (DCs) have been described in the tumor microenvironment in patients with cancer and tumor-bearing animals: (i) conventional DCs with intact antigen-presenting capabilities, (ii) functionally defective DCs with decreased motility and low ability to uptake, process and present antigens or produce cytokines and (iii) regulatory DCs with high capacity to suppress T cell proliferation, induce differentiation of regulatory T cells or support immune tolerance. Phenotypic characteristics of regulatory DCs (regDCs), as well as the mechanisms of T cell inhibition, vary in different experimental conditions and environments, suggesting high level of their plasticity and probably different origin. Although new data demonstrate that regDCs may play an important role at early stages of tumor development, functional differences and clinical significance of emergence of different myeloid regulatory cells (MDSCs, regDCs, M2 macrophages, N2 neutrophils, mast cells) in cancer remain to be determined.

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“…SHP-1 is primarily recognized as a negative regulator of signal transduction pathways in hematopoietic cells (32,33). For example, SHP-1 negatively regulates the signaling molecules activated by Ag (TCR, BCR) (34,35) and cytokine receptors (CSF-1, IFN-g, erythropoietin, c-Kit, IL-10) (36)(37)(38)(39)(40). Recently, we have shown a crucial and positive role for SHP-1 in LPS-mediated IL-6 production in SHP-1-null bone marrow-derived macrophages from motheaten (me/me) mice (41).…”

mentioning

confidence: 99%

SHP-1–Pyk2–Src Protein Complex and p38 MAPK Pathways Independently Regulate IL-10 Production in Lipopolysaccharide-Stimulated Macrophages

Okenwa

Kumar

Rego

et al. 2013

The Journal of Immunology

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The role of tyrosine phosphatase Src homology region 2 domain-containing phosphatase (SHP)-1 in LPS-activated cytokine production and inflammation was investigated by determining TNF-α and IL-10 production in splenic macrophages employing SHP-1–null (me/me) mouse model. LPS-stimulated me/me splenic macrophages secreted significantly less IL-10 with concomitantly elevated levels of TNF-α compared with wild-type (WT) macrophages irrespective of LPS dose and duration of stimulation. IL-10 significantly inhibited LPS-induced TNF-α production in both me/me and WT macrophages. The critical requirement for SHP-1 in regulating LPS-induced IL-10 and TNF-α production was confirmed by interfering with SHP-1 expression in WT macrophages and by reconstituting me/me macrophages with the SHP-1 gene. To delineate the role of SHP-1 in positive regulation of LPS-induced IL-10 production, signaling proteins representing SHP-1 targets were examined. The results reveal that tyrosine kinases Src and proline-rich tyrosine kinase 2 (Pyk2) regulate SHP-1–dependent LPS-induced IL-10 production and infer that optimal LPS-induced IL-10 production requires an assembly of a protein complex consisting of SHP-1–Pyk2–Src proteins. Moreover, LPS-induced IL-10 production also requires activation of the p38 MAPK independent of SHP-1 function. Overall, to our knowledge our results show for the first time that SHP-1 acts as a positive regulator of LPS-induced IL-10 production in splenic macrophages through two distinct and independent SHP-1–Pyk2–Src and p38 MAPK pathways.

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IL-10 inhibits CD28 and ICOS costimulations of T cells via src homology 2 domain—containing protein tyrosine phosphatase 1

Cited by 104 publications

References 35 publications

CD28 co‐signaling in the adaptive immune response

CD28 co‐signaling in the adaptive immune response

Immunosuppressive Mechanisms of Regulatory Dendritic Cells in Cancer

SHP-1–Pyk2–Src Protein Complex and p38 MAPK Pathways Independently Regulate IL-10 Production in Lipopolysaccharide-Stimulated Macrophages

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