SCART Scavenger Receptors Identify a Novel Subset of Adult γδ T Cells

Kisielow, Jan; Köpf, Manfred; Karjalainen, Klaus

doi:10.4049/jimmunol.181.3.1710

Cited by 106 publications

(121 citation statements)

References 33 publications

(36 reference statements)

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“…In concurrence, further reports showed that IL-17A-producing gd T cells do not express CD122 and CD27, while IFN-g-producing gd T cells stain positive for these markers [18,19]. In addition, SCART2 was identified as a positive determinant of thymic and peripheral gd T cells with the capacity to secrete IL-17A [20]. Collectively, these studies support the hypothesis that certain gd T-cell subsets acquire effector functions during thymic differentiation, which may be interpreted as a type of TCR-specific selection [21,22].…”

Section: Introductionmentioning

confidence: 57%

“…Such instructions could be encoded in TCR signals of differential strength. Kisielow et al elegantly showed that SCART2, a marker for thymic IL-17A-producing gd T cells, is expressed in deviated DN thymocytes of ab TCRtransgenic mice, but again downregulated in negatively selecting male HY mice [20]. Likewise, Kreslavsky et al have recently shown that a strong TCR-signal can induce the transcription factor PLZF which is required for the developmental progress from immature IL-17A-producing into IFN-g and IL-4-producing innate effector gd T cells [44].…”

Section: Discussionmentioning

confidence: 99%

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CCR6 and NK1.1 distinguish between IL‐17A and IFN‐γ‐producing γδ effector T cells

et al. 2009

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cd T cells are a potent source of innate IL-17A and IFN-c, and they acquire the capacity to produce these cytokines within the thymus. However, the precise stages and required signals that guide this differentiation are unclear. Here we show that the CD24 low CD44 high effector cd T cells of the adult thymus are segregated into two lineages by the mutually exclusive expression of CCR6 and NK1.1. Only CCR6 1 cd T cells produced IL-17A, while NK1.1 1 cd T cells were efficient producers of IFN-c but not of IL-17A. Their effector phenotype correlated with loss of CCR9 expression, particularly among the NK1.1 1 cd T cells. Accordingly, both cd T-cell subsets were rare in gut-associated lymphoid tissues, but abundant in peripheral lymphoid tissues. There, they provided IL-17A and IFN-c in response to TCR-specific and TCR-independent stimuli. IL-12 and IL-18 induced IFN-c and IL-23 induced IL-17A production by NK1.1 1 or CCR6 1 cd T cells, respectively. Importantly, we show that CCR6 1 cd T cells are more responsive to TCR stimulation than their NK1.1 1 counterparts. In conclusion, our findings support the hypothesis that CCR6 1 IL-17A-producing cd T cells derive from less TCR-dependent selection events than IFN-c-producing NK1.1 1 cd T cells.Key words: gd T cells . CCR6 . IFN-g . IL-17A . Innate lymphocytes . NK1.1 Introduction IL-17A and IFN-g are generally regarded as pro-inflammatory effector cytokines that can be produced by Th cells but also by innate lymphocytes such as NK cells, NKT cells and gd T cells. While macrophage activation is supposed to be the main role of IFN-g, the induction of granulopoiesis is ascribed as a key biological function of IL-17A [1]. It is currently emerging that gd T cells are a potent source of IL-17A in the early phases of immune responses (reviewed in [2]). gd T cells constitute a large fraction of all IL-17A-producing cells in healthy mice and humans and are able to secrete IL-17A much more rapidly than CD4 1 Th17 cells [3][4][5]. These observations led to the concept that gd T cells are important players in a transitional response between innate and adaptive immune reactions [6]. The production of innate IL-17A by gd T cells appears to be essential in situations where an effective defence against extra-cellular bacteria or fungi relies on the fast mobilization of neutrophils [4,[6][7][8][9]. Moreover, IL-17A-producing gd T cells have been described to play important roles in immunopathologic diseases such as collageninduced arthritis [10], experimental pulmonary fibrosis [11], and in experimental autoimmune encephalitis [12,13].In contrast to CD4 1 Th cells that can develop into Th17 cells after encounter of specific cognate TCR Ag [14][15][16], it is not clear which stimuli induce IL-17A production by gd T cells in vivo. This essentially results from a lack of information about physiological gd TCR ligands. However, the current literature suggests that the decision whether a gd T cell will produce IL-17A is linked to 3488thymic development. Jensen et al. introduced a concept th...

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Section: Introductionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

CCR6 and NK1.1 distinguish between IL‐17A and IFN‐γ‐producing γδ effector T cells

et al. 2009

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“…Although IL‐23R is constitutively expressed on γδ 17 cells, the expression of IL‐1R in peripheral γδ 17 cells is tissue‐dependent 48. In addition to IL‐1R and IL‐23R, the expression of scavenger receptor 2 (Scart 2)49 and CCR6,27 and the lack of CD12225 and CD27 expression26 are often used as markers for γδ 17 cells, with the exception for IL‐17‐producing V γ 1 + γδ T cells 33. These phenotypes, established during thymic development, distinguish γδ 17 cells from IFN‐γ‐producing γδ T ( γδ IFN‐ γ ) cells (Fig.…”

Section: γδ T‐cell Subsets and Their Developmentmentioning

confidence: 99%

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

Akitsu

Iwakura

2018

Immunology

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SummaryInterleukin‐17 (IL‐17) is a pro‐inflammatory cytokine and is involved in the development of many diseases. Recent studies have revealed that IL‐17‐producing γδ T cells (γδ17 cells) in addition to IL‐17‐producing CD4+ T cells [T helper type 17 (Th17) cells] are often the main producers of IL‐17 in mouse models of inflammatory diseases. γδ T cells are functionally committed during intra‐thymic differentiation. γδ thymocytes capable of producing IL‐17, which express the transcription factor retinoic‐acid‐receptor‐related orphan receptor γt and the signature cytokine receptor IL‐23R, leave the thymus, and produce IL‐17 rapidly by the stimulation with IL‐1β and IL‐23 in the periphery. Therefore, γδ17 cells play important roles in the early phase of host defence against pathogens and in inflammatory diseases. γδ T cells that can produce IL‐17 are also increased in the skin of patients with psoriasis and in peripheral blood of patients with ankylosing sclerosis. Indeed, the therapy targeting IL‐17 has been approved or is in clinical trials, and proved to be very efficient to treat psoriasis, psoriatic arthritis and ankylosing sclerosis. In this review, we discuss recent knowledge about the pathophysiological function of γδ17 cells in infection and inflammatory diseases and therapeutic advances targeting IL‐17.

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“…In recent years, a number of studies also supported the recognition of PAMPs by some, but not all, group A (i.e., MARCO) (15) and B (i.e., DMBT1/SAG/gp340, Spa, CD6, CD5, and CD163) (16)(17)(18)(19)(20) SRCR-SF members. Group B is composed of about a dozen members expressed in mammals by immune cells, such as macrophages (i.e., CD163/M130, CD163L1/M160, Spa/AIM) or lymphocytes (i.e., CD5, CD6, SCART, WC1), as well as by cells of the gastrointestinal, respiratory, and genitourinary tracts (i.e., DMBT1/ SAG/gp340, S4D-SRCRB, 18-B) (5,21). The present work reports on the characterization, at the molecular and functional levels, of S5D-SRCRB (soluble 5 domain SRCR type B), the mouse homolog of a recently cloned human soluble member belonging to group B of SRCR-SF (SSc5D), for which no biochemical and functional data are available (22).…”

mentioning

confidence: 99%

Molecular and Functional Characterization of Mouse S5D-SRCRB: A New Group B Member of the Scavenger Receptor Cysteine-Rich Superfamily

Miró-Julià

Roselló

Martínez

et al. 2011

The Journal of Immunology

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The scavenger receptor cysteine-rich superfamily (SRCR-SF) members are transmembrane and/or secreted receptors exhibiting one or several repeats of a cysteine-rich protein module of ∼100 aa, named scavenger receptor cysteine-rich (SRCR). Two types of SRCR domains (A or B) have been reported, which differ in the number of coding exons and intradomain cysteines. Although no unifying function has been reported for SRCR-SF members, recognition of pathogen-associated molecular patterns (PAMPs) was recently shown for some of them. In this article, we report the structural and functional characterization of mouse S5D-SRCRB, a new group B member of the SRCR-SF. The s5d-srcrb gene maps at mouse chromosome 7 and encompasses 14 exons extending over 15 kb. The longest cDNA sequence found is 4286 bp in length and encodes a mature protein of 1371 aa, with a predicted Mr of 144.6 kDa. Using an episomal mammalian-expression system, a glycosylated soluble recombinant form >200 kDa was obtained and used as immunogen for the generation of specific rat mAbs. Subsequent immunohistochemical and real-time PCR analysis showed significant S5D-SRCRB expression in murine genitourinary and digestive tracts. S5D-SRCRB was shown to bind endogenous extracellular matrix proteins (laminin and galectin-1), as well as PAMPs present on Gram-positive and Gram-negative bacteria and fungi. PAMP binding by S5D-SRCRB induced microbial aggregation and subsequent inhibition of PAMP-induced cytokine release. These abilities suggest that S5D-SRCRB might play a role in the innate defense and homeostasis of certain specialized epithelial surfaces.

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SCART Scavenger Receptors Identify a Novel Subset of Adult γδ T Cells

Cited by 106 publications

References 33 publications

CCR6 and NK1.1 distinguish between IL‐17A and IFN‐γ‐producing γδ effector T cells

CCR6 and NK1.1 distinguish between IL‐17A and IFN‐γ‐producing γδ effector T cells

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

Molecular and Functional Characterization of Mouse S5D-SRCRB: A New Group B Member of the Scavenger Receptor Cysteine-Rich Superfamily

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