Synthetic Retinoid AM80 Inhibits Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis

Klemann, Christian; Raveney, Ben J. E.; Klemann, Anna K.; Ozawa, Tomoko; Hörsten, Stephan von; Shudo, Koichi; Oki, Sadaaki; Yamamura, Takashi

doi:10.2353/ajpath.2009.081084

Cited by 84 publications

(75 citation statements)

References 54 publications

(81 reference statements)

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“…Finally, in order to strength the link between RORC and CD161, we cultured Th17 clones in the presence or in the absence of a synthetic RAR agonist, AM80, which has been shown to inhibit Th17 differentiation by suppressing RORC [26]. In agreement with the previous results [26], RORC as well as IL-17 expression was significantly suppressed on Th17 clones at both mRNA and protein levels in the presence of AM80 when assessed 3 and 7 days after in vitro culturing (Fig. 3D and data not shown).…”

Section: Cells Transduction With a Rorc2-viral Vector Results In Indumentioning

confidence: 99%

CD161 is a marker of all human IL‐17‐producing T‐cell subsets and is induced by RORC

et al. 2010

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We have previously shown that human Th17 lymphocytes are characterized by the selective expression of IL-23 receptor (IL-23R), CCR6, CD161, and the transcription factor retinoic acid-related orphan receptor C (RORC), and originate from a CD161 1 CD41 naïve T-cell precursor in response to the combined activity of IL-1b and IL-23. We show here that not only CD4 CD161À T cells, upon lentivirusmediated transduction with RORC2 can acquire the ability to express IL-23R, IL-1RI, and CD161, as well as to produce IL-17. Taken together, these data allow to conclude that T-cell subsets able to produce IL-17, as well as precursors of IL-17-producing T cells, exhibit surface expression of CD161, and that this feature is at least in part RORC2-dependent.

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Section: Cells Transduction With a Rorc2-viral Vector Results In Indumentioning

confidence: 99%

CD161 is a marker of all human IL‐17‐producing T‐cell subsets and is induced by RORC

et al. 2010

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“…Staining was carried out according to standard protocols as previously described (40). In brief, fixable Viability Dye (eBioscience, San Diego, CA) was used to exclude dead cells, and the following antibodies (all purchased from eBioscience) were employed for staining in the…”

Section: Flow Cytometrymentioning

confidence: 99%

The viral dsRNA analogue poly (I:C) induces necrotizing enterocolitis in neonatal mice

Ginzel

Klemann

et al. 2015

Pediatr Res

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Background: Necrotizing enterocolitis (NEC) is a lifethreatening gastrointestinal disease in premature infants with high mortality and morbidity with uncertain pathogenesis. Recent research focused on the role of intraluminal bacteria and lipopolysaccharide (LPS). However, an additional role of viral agents in the pathogenesis of NEC has recently been postulated. We assessed the role of polyinosinic:polycytidylic acid (pIC) mimicking viral dsRNA in contributing to the development of NEC in neonatal mice. Methods: Four-d-old C57BL/6J pups were stressed by asphyxia and hypothermia twice daily. Animals were either fed by formula only (FO), formula containing LPS or pIC. After 72 h, mice were euthanized, intestines harvested, and the severity of NEC was assessed. results: Breastfed mice showed no evidence of NEC. Very mild NEC-like lesions were observed in mice fed by FO. Supplementation of LPS or pIC to the formula led to increased intestinal tissue damage and inflammation compared with FO in a similar manner. conclusion: Our study demonstrates the ability of viral factors to induce NEC in neonatal mice even in the absence of LPS. Furthermore, we present a new mouse model of pIC-induced NEC which may be used to obtain further mechanistic insights in the pathogenesis of this disease.

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“…Such an effect was correlated with lower IL-10 production during disease progression. However, continuous administration failed to inhibit late EAE symptoms (99).…”

Section: Ra Regulates Experimental Autoimmune Encephalomyelitismentioning

confidence: 99%

Leukocyte Homing, Fate, and Function Are Controlled by Retinoic Acid

Guo

Brown

Ortiz

et al. 2015

Physiological Reviews

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Although vitamin A was recognized as an "anti-infective vitamin" over 90 years ago, the mechanism of how vitamin A regulates immunity is only beginning to be understood. Early studies which focused on the immune responses in vitamin A-deficient (VAD) animals clearly demonstrated compromised immunity and consequently increased susceptibility to infectious disease. The active form of vitamin A, retinoic acid (RA), has been shown to have a profound impact on the homing and differentiation of leukocytes. Both pharmacological and genetic approaches have been applied to the understanding of how RA regulates the development and differentiation of various immune cell subsets, and how RA influences the development of immunity versus tolerance. These studies clearly show that RA profoundly impacts on cell-and humoralmediated immunity. In this review, the early findings on the complex relationship between VAD and immunity are discussed as well as vitamin A metabolism and signaling within hematopoietic cells. Particular attention is focused on how RA impacts on T-cell lineage commitment and plasticity in various diseases.

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Synthetic Retinoid AM80 Inhibits Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis

Cited by 84 publications

References 54 publications

CD161 is a marker of all human IL‐17‐producing T‐cell subsets and is induced by RORC

CD161 is a marker of all human IL‐17‐producing T‐cell subsets and is induced by RORC

The viral dsRNA analogue poly (I:C) induces necrotizing enterocolitis in neonatal mice

Leukocyte Homing, Fate, and Function Are Controlled by Retinoic Acid

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