A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system.
While the immune system is essential for the maintenance of the homeostasis, health and survival of humans, aberrant immune responses can lead to chronic inflammatory and autoimmune disorders. Pharmacological modulation of drug targets in the immune system to ameliorate disease also carry a risk of...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5515432?pdf=render |
| _version_ | 1819105514743660544 |
|---|---|
| author | Cristina St Pierre Jane Guo John D Shin Laura W Engstrom Hyun-Hee Lee Alan Herbert Laura Surdi James Baker Michael Salmon Sanjiv Shah J Michael Ellis Hani Houshyar Michael A Crackower Melanie A Kleinschek Dallas C Jones Alexandra Hicks Dennis M Zaller Stephen E Alves Ravisankar A Ramadas |
| author_facet | Cristina St Pierre Jane Guo John D Shin Laura W Engstrom Hyun-Hee Lee Alan Herbert Laura Surdi James Baker Michael Salmon Sanjiv Shah J Michael Ellis Hani Houshyar Michael A Crackower Melanie A Kleinschek Dallas C Jones Alexandra Hicks Dennis M Zaller Stephen E Alves Ravisankar A Ramadas |
| author_sort | Cristina St Pierre |
| collection | DOAJ |
| description | While the immune system is essential for the maintenance of the homeostasis, health and survival of humans, aberrant immune responses can lead to chronic inflammatory and autoimmune disorders. Pharmacological modulation of drug targets in the immune system to ameliorate disease also carry a risk of immunosuppression that could lead to adverse outcomes. Therefore, it is important to understand the 'immune fingerprint' of novel therapeutics as they relate to current and, clinically used immunological therapies to better understand their potential therapeutic benefit as well as immunosuppressive ability that might lead to adverse events such as infection risks and cancer. Since the mechanistic investigation of pharmacological modulators in a drug discovery setting is largely compound- and mechanism-centric but not comprehensive in terms of immune system impact, we developed a human tissue based functional assay platform to evaluate the impact of pharmacological modulators on a range of innate and adaptive immune functions. Here, we demonstrate that it is possible to generate a qualitative and quantitative immune system impact of pharmacological modulators, which might help better understand and predict the benefit-risk profiles of these compounds in the treatment of immune disorders. |
| first_indexed | 2024-12-22T02:23:28Z |
| format | Article |
| id | doaj.art-a511e5553a1e4c19982a055d21745012 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T02:23:28Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a511e5553a1e4c19982a055d217450122022-12-21T18:42:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01127e018087010.1371/journal.pone.0180870A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system.Cristina St PierreJane GuoJohn D ShinLaura W EngstromHyun-Hee LeeAlan HerbertLaura SurdiJames BakerMichael SalmonSanjiv ShahJ Michael EllisHani HoushyarMichael A CrackowerMelanie A KleinschekDallas C JonesAlexandra HicksDennis M ZallerStephen E AlvesRavisankar A RamadasWhile the immune system is essential for the maintenance of the homeostasis, health and survival of humans, aberrant immune responses can lead to chronic inflammatory and autoimmune disorders. Pharmacological modulation of drug targets in the immune system to ameliorate disease also carry a risk of immunosuppression that could lead to adverse outcomes. Therefore, it is important to understand the 'immune fingerprint' of novel therapeutics as they relate to current and, clinically used immunological therapies to better understand their potential therapeutic benefit as well as immunosuppressive ability that might lead to adverse events such as infection risks and cancer. Since the mechanistic investigation of pharmacological modulators in a drug discovery setting is largely compound- and mechanism-centric but not comprehensive in terms of immune system impact, we developed a human tissue based functional assay platform to evaluate the impact of pharmacological modulators on a range of innate and adaptive immune functions. Here, we demonstrate that it is possible to generate a qualitative and quantitative immune system impact of pharmacological modulators, which might help better understand and predict the benefit-risk profiles of these compounds in the treatment of immune disorders.http://europepmc.org/articles/PMC5515432?pdf=render |
| spellingShingle | Cristina St Pierre Jane Guo John D Shin Laura W Engstrom Hyun-Hee Lee Alan Herbert Laura Surdi James Baker Michael Salmon Sanjiv Shah J Michael Ellis Hani Houshyar Michael A Crackower Melanie A Kleinschek Dallas C Jones Alexandra Hicks Dennis M Zaller Stephen E Alves Ravisankar A Ramadas A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system. PLoS ONE |
| title | A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system. |
| title_full | A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system. |
| title_fullStr | A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system. |
| title_full_unstemmed | A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system. |
| title_short | A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system. |
| title_sort | human tissue based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system |
| url | http://europepmc.org/articles/PMC5515432?pdf=render |
| work_keys_str_mv | AT cristinastpierre ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT janeguo ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT johndshin ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT laurawengstrom ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT hyunheelee ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT alanherbert ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT laurasurdi ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT jamesbaker ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT michaelsalmon ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT sanjivshah ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT jmichaelellis ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT hanihoushyar ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT michaelacrackower ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT melanieakleinschek ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT dallascjones ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT alexandrahicks ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT dennismzaller ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT stephenealves ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT ravisankararamadas ahumantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT cristinastpierre humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT janeguo humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT johndshin humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT laurawengstrom humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT hyunheelee humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT alanherbert humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT laurasurdi humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT jamesbaker humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT michaelsalmon humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT sanjivshah humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT jmichaelellis humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT hanihoushyar humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT michaelacrackower humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT melanieakleinschek humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT dallascjones humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT alexandrahicks humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT dennismzaller humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT stephenealves humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem AT ravisankararamadas humantissuebasedfunctionalassayplatformtoevaluatetheimmunefunctionimpactofsmallmoleculeinhibitorsthattargettheimmunesystem |