Tryptophan (W) at position 37 of murine IL-12/IL-23 p40 is mandatory for binding to IL-12Rβ1 and subsequent signal transduction

Georgy, Jacqueline; Arlt, Yvonne; Moll, Jens M.; Ouzin, Meryem; Weitz, Hendrik T.; Gremer, Lothar; Willbold, Dieter; Grötzinger, Joachim; Thives-Kurenbach, Felix; Scheller, Jürgen; Floß, Doreen M.

doi:10.1016/j.jbc.2021.101295

Cited by 8 publications

(4 citation statements)

References 28 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the pleiotropic immunoregulatory landscape for IL-12 and IL-23, including their role in physiology and disease, have been examined in detail over the past 2 decades ( Wojno et al., 2019 ), our understanding of the structural determinants for the assembly of their promiscuous receptor complexes is incomplete. The current view has been derived from recent structural breakthroughs on complexes mediated by IL-23 and IL-12 ( Bloch et al., 2018 ; Glassman et al., 2021 ), and structure-driven mechanistic interrogation ( Esch et al., 2020 ; Floss et al., 2020 ; Georgy et al., 2021 ). However, it is now clear that this cannot universally apply to the entire family due to fundamental differences in the type and pairing of α- and β-cytokine subunits and the domain organization and pairing of receptors.…”

Section: Introductionmentioning

confidence: 99%

Structural basis of activation and antagonism of receptor signaling mediated by interleukin-27

Składanowska

Bloch

Strand³

et al. 2022

Cell Reports

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Structural basis of activation and antagonism of receptor signaling mediated by interleukin-27

Składanowska

Bloch

Strand³

et al. 2022

Cell Reports

View full text Add to dashboard Cite

“…The mucosal increase in IL-12 during intestinal inflammation has also been observed [54]. It has been shown that SER, HIS and TYR are required for IL-2 binding and biological activity, and that ASP, THR, and TRP are among the important amino acids for the interaction of IL-12 with its receptor [55]. Therefore, controlling these residues may have the potential to be considered a therapeutic target for CD patients, but this needs to be confirmed in further studies [56,57].…”

Section: Discussionmentioning

confidence: 93%

Investigating the Impact of Vitamin A and Amino Acids on Immune Responses in Celiac Disease Patients

Fallah,

Asri,

Nikzamir

et al. 2024

Diseases

View full text Add to dashboard Cite

Amino acids (AAs) and vitamin imbalances are observed in celiac disease (CD). This study evaluated the plasma profile of vitamin A and AAs and the expression level of IL-2, IL-4, IL-10, IL-12 and TGFβ in CD patients. A total of 60 children and adults with CD and 40 healthy controls (HCs) were included. The plasma profile of Vitamin A and AAs and the mRNA expression levels of target genes were assessed. Active adult patients exhibited a decrease in Vitamin A levels (p = 0.04) and an increase in IL-2 (p = 0.008) and IL-12 (p = 0.007) mRNA expression compared to the HCs. The treated adult patients showed elevated Serine (p = 0.003) and Glycine (p = 0.04) levels, as well as increased IL-12 (p < 0.0001) mRNA expression, and a decrease in Tryptophan (p = 0.04) levels relative to the controls. Additionally, the treated adult patients had higher plasma levels of Threonine compared to both the active (p = 0.04) and control (p = 0.02) subjects, and the increased mRNA expression of IL-4 (p = 0.01) in comparison to the active patients. In active children with CD, the IL-2 mRNA level was found to be higher than in the controls (p < 0.0001) and in the treated children (p = 0.005). The treated children with CD exhibited decreased plasma levels of Tryptophan (p = 0.01) and Isoleucine (p = 0.01) relative to the controls, and the increased mRNA expression of TGFβ (p = 0.04) relative to the active patients. Elevated levels of specific AAs (Serine, Glycine, Threonine) in the treated CD patients suggested their potential to improve intestinal damage and inflammation, while decreased levels of Tryptophan and Isoleucine highlighted the need for dietary intervention.

show abstract

“…The mucosal increase of IL-12 during intestinal inflammation has also been observed [66]. It has been shown that SER, HIS and TYR are required for IL-2 binding and biological activity, and ASP, THR, and TRP are among the important amino acids for the interaction of IL-12 with its receptor [67]. So might controlling these residues have the potential to be considered as therapeutic targets for CD patients, which needs to be approved in further studies [68].…”

Section: Discussionmentioning

confidence: 95%

Altered Peripheral Amino Acid Profile Has Pivotal Role in Controlling Pro- and anti- Inflammatory Responses in Celiac Disease

Fallah,

Asri,

Nikzamir

et al. 2023

Preprint

View full text Add to dashboard Cite

The amino acids (AAs) and vitamins imbalances are observed in celiac disease (CD). This study evaluated the plasma profile of vitamin A and AAs and the expression level of IL-2, IL-4, IL-10, IL-12 and TGFβ in CD patients. A total of 60 children and adults with CD and 40 healthy controls (HCs) were included. Plasma profile of Vitamin A and AAs and the mRNA expression levels of target genes were assessed. Active adult patients exhibited a decrease in Vitamin A levels (p=0.04) and an increase in IL-2 (p=0.008) and IL-12 (p=0.007) mRNA expression compared to HCs. Treated adult patients showed elevated Serine (p=0.003) and Glycin (p=0.04) levels, as well as increased IL-12 (P&lt;0.0001) mRNA expression, and a decrease in Tryptophan (p=0.04) levels relative to the controls. Additionally, treated adult patients had higher plasma levels of Threonine compared to both active (p=0.04) and control (p=0.02) subjects, and increased mRNA expression of IL-4 (p=0.01) in comparison to active patients. In active children with CD, IL-2 mRNA level was found to be higher than in controls (P&lt;0.0001) and in treated children (p=0.005). Treated children with CD exhibited decreased plasma levels of Tryptophan (p=0.01) and Isoleucine (p=0.01) relative to the controls, and increased mRNA expression of TGFβ (p=0.04) relative to active patients. Managing Retinoic acid levels is crucial to alleviate intestinal inflammation of CD patients. Threonine, tryptophan, and Isoleucine are potential therapeutic options for treating CD, and targeting serine, histidine, tyrosine, and aspartate may hold promise as therapeutic targets for CD patients.

show abstract

Tryptophan (W) at position 37 of murine IL-12/IL-23 p40 is mandatory for binding to IL-12Rβ1 and subsequent signal transduction

Cited by 8 publications

References 28 publications

Structural basis of activation and antagonism of receptor signaling mediated by interleukin-27

Structural basis of activation and antagonism of receptor signaling mediated by interleukin-27

Investigating the Impact of Vitamin A and Amino Acids on Immune Responses in Celiac Disease Patients

Altered Peripheral Amino Acid Profile Has Pivotal Role in Controlling Pro- and anti- Inflammatory Responses in Celiac Disease

Contact Info

Product

Resources

About