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Revisiting the combinatorial potential of cytokine subunits in the IL-12 family

(2019) BIOCHEMICAL PHARMACOLOGY. 165. p.240-248
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Abstract
The four core members of the Interleukin-12 (IL-12) family of cytokines, IL-12, IL-23, IL-27 and IL-35 are heterodimers which share alpha- and beta-cytokine subunits. All four cytokines are immune modulators and have been proposed to play divergent roles in inflammatory arthritis. In recent years additional combinations of alpha- and beta-cytokine subunits belonging to the IL-12 family have been proposed to form novel cytokines such as IL-39. However, the actual extent of the combinatorial potential of the cytokine subunits in the human IL-12 family is not known. Here, we identify several combinations of subunits that form secreted heterodimeric assemblies based on a systematic orthogonal approach. The heterodimers are detected in the conditioned media harvested from mammalian cell cultures transfected with unfused pairs of cytokine subunits. While certain previously reported subunit combinations could not be recapitulated, our approach showed robustly that all four of the canonical members could be secreted. Furthermore, we provide evidence for the interaction between Cytokine Receptor Like Factor 1 (CRLF1) and Interleukin-12 subunit alpha (p35). Similar to IL-27 and IL-35 this novel heterodimer is not abundantly secreted rendering isolation from the conditioned medium very challenging, unlike IL-12 and IL-23. Our findings set the stage for fine-tuning approaches towards the biochemical reconstitution of IL-12 family cytokines for biochemical, cellular, and structural studies.
Keywords
UNFOLDED PROTEIN RESPONSE, HETERODIMERIC CYTOKINE, IL-23, PSORIASIS, IMMUNITY, DISTINCT, GENES, Cytokines, Inflammation, Interleukin, Heterodimer, IL-12 family

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Citation

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MLA
Detry, Sammy, et al. “Revisiting the Combinatorial Potential of Cytokine Subunits in the IL-12 Family.” BIOCHEMICAL PHARMACOLOGY, vol. 165, 2019, pp. 240–48.
APA
Detry, S., Skladanowska, K., Vuylsteke, M., Savvides, S., & Bloch, Y. (2019). Revisiting the combinatorial potential of cytokine subunits in the IL-12 family. BIOCHEMICAL PHARMACOLOGY, 165, 240–248.
Chicago author-date
Detry, Sammy, Katarzyna Skladanowska, Marnik Vuylsteke, Savvas Savvides, and Yehudi Bloch. 2019. “Revisiting the Combinatorial Potential of Cytokine Subunits in the IL-12 Family.” BIOCHEMICAL PHARMACOLOGY 165: 240–48.
Chicago author-date (all authors)
Detry, Sammy, Katarzyna Skladanowska, Marnik Vuylsteke, Savvas Savvides, and Yehudi Bloch. 2019. “Revisiting the Combinatorial Potential of Cytokine Subunits in the IL-12 Family.” BIOCHEMICAL PHARMACOLOGY 165: 240–248.
Vancouver
1.
Detry S, Skladanowska K, Vuylsteke M, Savvides S, Bloch Y. Revisiting the combinatorial potential of cytokine subunits in the IL-12 family. BIOCHEMICAL PHARMACOLOGY. 2019;165:240–8.
IEEE
[1]
S. Detry, K. Skladanowska, M. Vuylsteke, S. Savvides, and Y. Bloch, “Revisiting the combinatorial potential of cytokine subunits in the IL-12 family,” BIOCHEMICAL PHARMACOLOGY, vol. 165, pp. 240–248, 2019.
@article{8625672,
  abstract     = {The four core members of the Interleukin-12 (IL-12) family of cytokines, IL-12, IL-23, IL-27 and IL-35 are heterodimers which share alpha- and beta-cytokine subunits. All four cytokines are immune modulators and have been proposed to play divergent roles in inflammatory arthritis. In recent years additional combinations of alpha- and beta-cytokine subunits belonging to the IL-12 family have been proposed to form novel cytokines such as IL-39. However, the actual extent of the combinatorial potential of the cytokine subunits in the human IL-12 family is not known. Here, we identify several combinations of subunits that form secreted heterodimeric assemblies based on a systematic orthogonal approach. The heterodimers are detected in the conditioned media harvested from mammalian cell cultures transfected with unfused pairs of cytokine subunits. While certain previously reported subunit combinations could not be recapitulated, our approach showed robustly that all four of the canonical members could be secreted. Furthermore, we provide evidence for the interaction between Cytokine Receptor Like Factor 1 (CRLF1) and Interleukin-12 subunit alpha (p35). Similar to IL-27 and IL-35 this novel heterodimer is not abundantly secreted rendering isolation from the conditioned medium very challenging, unlike IL-12 and IL-23. Our findings set the stage for fine-tuning approaches towards the biochemical reconstitution of IL-12 family cytokines for biochemical, cellular, and structural studies.},
  author       = {Detry, Sammy and Skladanowska, Katarzyna and Vuylsteke, Marnik and Savvides, Savvas and Bloch, Yehudi},
  issn         = {0006-2952},
  journal      = {BIOCHEMICAL PHARMACOLOGY},
  keywords     = {UNFOLDED PROTEIN RESPONSE,HETERODIMERIC CYTOKINE,IL-23,PSORIASIS,IMMUNITY,DISTINCT,GENES,Cytokines,Inflammation,Interleukin,Heterodimer,IL-12 family},
  language     = {eng},
  pages        = {240--248},
  title        = {Revisiting the combinatorial potential of cytokine subunits in the IL-12 family},
  url          = {http://dx.doi.org/10.1016/j.bcp.2019.03.026},
  volume       = {165},
  year         = {2019},
}

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