Adenoviral gene transfer of a single-chain IL-23 induces psoriatic arthritis–like symptoms in NOD mice

Rafael R. Flores; Lana Carbo; Eun Kim; Montina Van Meter; Consuelo M.Lopez De Padilla; Jing Zhao; Debora Colangelo; Matthew J. Yousefzadeh; Luise A. Angelini; Lei Zhang; Enrico Pola; Nam Vo; Christopher H. Evans; Andrea Gambotto; Laura J. Niedernhofer; Paul D. Robbins

doi:10.1096/fj.201900420R

Adenoviral gene transfer of a single-chain IL-23 induces psoriatic arthritis–like symptoms in NOD mice

Rafael R. Flores, Lana Carbo, Eun Kim, Montina Van Meter, Consuelo M.Lopez De Padilla, Jing Zhao, Debora Colangelo, Matthew J. Yousefzadeh, Luise A. Angelini, Lei Zhang, Enrico Pola, Nam Vo, Christopher H. Evans, Andrea Gambotto, Laura J. Niedernhofer, Paul D. Robbins

Biochemistry, Molecular Biology, and Biophysics (TMED)

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Previously, we demonstrated that intratumoral delivery of adenoviral vector encoding single-chain (sc) IL-23 (Ad.scIL-23) was able to induce systemic antitumor immunity. Here, we examined the role of IL-23 in diabetes in nonobese diabetic mice. Intravenous delivery of Ad.scIL-23 did not accelerate the onset of hyperglycemia but instead resulted in the development of psoriatic arthritis. Ad.scIL-23–treated mice developed erythema, scales, and thickening of the skin, as well as intervertebral disc degeneration and extensive synovial hypertrophy and loss of articular cartilage in the knees. Immunological analysis revealed activation of conventional T helper type 17 cells and IL-17–producing γδ T cells along with a significant depletion and suppression of T cells in the pancreatic lymph nodes. Furthermore, treatment with anti–IL-17 antibody reduced joint and skin psoriatic arthritis pathologies. Thus, these Ad.scIL-23–treated mice represent a physiologically relevant model of psoriatic arthritis for understanding disease progression and for testing therapeutic approaches.—Flores, R. R., Carbo, L., Kim, E., Van Meter, M., De Padilla, C. M. L., Zhao, J., Colangelo, D., Yousefzadeh, M. J., Angelini, L. A., Zhang, L., Pola, E., Vo, N., Evans, C. H., Gambotto, A., Niedernhofer, L. J., Robbins, P. D. Adenoviral gene transfer of a single-chain IL-23 induces psoriatic arthritis–like symptoms in NOD mice. FASEB J. 33, 9505–9515 (2019). www.fasebj.org.

Original language	English (US)
Pages (from-to)	9505-9515
Number of pages	11
Journal	FASEB Journal
Volume	33
Issue number	8
DOIs	https://doi.org/10.1096/fj.201900420R
State	Published - Aug 1 2019

Bibliographical note

Funding Information:
The authors thank Biviana Torres (The Scripps Research Institute) for her assistance with flow cytometry and Shannon Howard, Sara McGowan, and Tokio Sano (all from The Scripps Research Institute) for their assistance in collecting and the processing of tissues. The authors acknowledge and extend gratitude to Yuan Yuan Ling (retired, formerly of The Scripps Research Institute) for years of service to science. This work was supported by Grants from the U.S. National Institutes of Health (NIH) National Institute on Aging (AG024827, AG044376), NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR051456), and a program grant from the Juvenile Diabetes Research Foundation to P.D.R. R.R.F. was supported by a T32 grant from NIH on Autoimmunity and Immunopathology. This project used the University of Pittsburgh Cancer Institute Vector Facilities (Pittsburgh, PA, USA) supported by the University of Pittsburgh's NIH Cancer Center Support Grant P30 CA047904. The authors declare no conflicts of interest.

Publisher Copyright:
© FASEB

Keywords

adenovirus
interleukin-17
interleukin-23
psoriasis
type 1 diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access

10.1096/fj.201900420R

OpenUrl availability

Full text

Cite this

Flores, R. R., Carbo, L., Kim, E., Van Meter, M., De Padilla, C. M. L., Zhao, J., Colangelo, D., Yousefzadeh, M. J., Angelini, L. A., Zhang, L., Pola, E., Vo, N., Evans, C. H., Gambotto, A., Niedernhofer, L. J., & Robbins, P. D. (2019). Adenoviral gene transfer of a single-chain IL-23 induces psoriatic arthritis–like symptoms in NOD mice. FASEB Journal, 33(8), 9505-9515. https://doi.org/10.1096/fj.201900420R

Flores, RR, Carbo, L, Kim, E, Van Meter, M, De Padilla, CML, Zhao, J, Colangelo, D, Yousefzadeh, MJ, Angelini, LA, Zhang, L, Pola, E, Vo, N, Evans, CH, Gambotto, A, Niedernhofer, LJ & Robbins, PD 2019, 'Adenoviral gene transfer of a single-chain IL-23 induces psoriatic arthritis–like symptoms in NOD mice', FASEB Journal, vol. 33, no. 8, pp. 9505-9515. https://doi.org/10.1096/fj.201900420R

@article{7bcedd98e3a6490d8c7f6f489b5de543,

title = "Adenoviral gene transfer of a single-chain IL-23 induces psoriatic arthritis–like symptoms in NOD mice",

abstract = "Previously, we demonstrated that intratumoral delivery of adenoviral vector encoding single-chain (sc) IL-23 (Ad.scIL-23) was able to induce systemic antitumor immunity. Here, we examined the role of IL-23 in diabetes in nonobese diabetic mice. Intravenous delivery of Ad.scIL-23 did not accelerate the onset of hyperglycemia but instead resulted in the development of psoriatic arthritis. Ad.scIL-23–treated mice developed erythema, scales, and thickening of the skin, as well as intervertebral disc degeneration and extensive synovial hypertrophy and loss of articular cartilage in the knees. Immunological analysis revealed activation of conventional T helper type 17 cells and IL-17–producing γδ T cells along with a significant depletion and suppression of T cells in the pancreatic lymph nodes. Furthermore, treatment with anti–IL-17 antibody reduced joint and skin psoriatic arthritis pathologies. Thus, these Ad.scIL-23–treated mice represent a physiologically relevant model of psoriatic arthritis for understanding disease progression and for testing therapeutic approaches.—Flores, R. R., Carbo, L., Kim, E., Van Meter, M., De Padilla, C. M. L., Zhao, J., Colangelo, D., Yousefzadeh, M. J., Angelini, L. A., Zhang, L., Pola, E., Vo, N., Evans, C. H., Gambotto, A., Niedernhofer, L. J., Robbins, P. D. Adenoviral gene transfer of a single-chain IL-23 induces psoriatic arthritis–like symptoms in NOD mice. FASEB J. 33, 9505–9515 (2019). www.fasebj.org.",

keywords = "adenovirus, interleukin-17, interleukin-23, psoriasis, type 1 diabetes",

author = "Flores, {Rafael R.} and Lana Carbo and Eun Kim and {Van Meter}, Montina and {De Padilla}, {Consuelo M.Lopez} and Jing Zhao and Debora Colangelo and Yousefzadeh, {Matthew J.} and Angelini, {Luise A.} and Lei Zhang and Enrico Pola and Nam Vo and Evans, {Christopher H.} and Andrea Gambotto and Niedernhofer, {Laura J.} and Robbins, {Paul D.}",

note = "Funding Information: The authors thank Biviana Torres (The Scripps Research Institute) for her assistance with flow cytometry and Shannon Howard, Sara McGowan, and Tokio Sano (all from The Scripps Research Institute) for their assistance in collecting and the processing of tissues. The authors acknowledge and extend gratitude to Yuan Yuan Ling (retired, formerly of The Scripps Research Institute) for years of service to science. This work was supported by Grants from the U.S. National Institutes of Health (NIH) National Institute on Aging (AG024827, AG044376), NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR051456), and a program grant from the Juvenile Diabetes Research Foundation to P.D.R. R.R.F. was supported by a T32 grant from NIH on Autoimmunity and Immunopathology. This project used the University of Pittsburgh Cancer Institute Vector Facilities (Pittsburgh, PA, USA) supported by the University of Pittsburgh's NIH Cancer Center Support Grant P30 CA047904. The authors declare no conflicts of interest. Publisher Copyright: {\textcopyright} FASEB",

year = "2019",

month = aug,

day = "1",

doi = "10.1096/fj.201900420R",

language = "English (US)",

volume = "33",

pages = "9505--9515",

journal = "FASEB Journal",

issn = "0892-6638",

publisher = "FASEB",

number = "8",

}

TY - JOUR

T1 - Adenoviral gene transfer of a single-chain IL-23 induces psoriatic arthritis–like symptoms in NOD mice

AU - Flores, Rafael R.

AU - Carbo, Lana

AU - Kim, Eun

AU - Van Meter, Montina

AU - De Padilla, Consuelo M.Lopez

AU - Zhao, Jing

AU - Colangelo, Debora

AU - Yousefzadeh, Matthew J.

AU - Angelini, Luise A.

AU - Zhang, Lei

AU - Pola, Enrico

AU - Vo, Nam

AU - Evans, Christopher H.

AU - Gambotto, Andrea

AU - Niedernhofer, Laura J.

AU - Robbins, Paul D.

N1 - Funding Information: The authors thank Biviana Torres (The Scripps Research Institute) for her assistance with flow cytometry and Shannon Howard, Sara McGowan, and Tokio Sano (all from The Scripps Research Institute) for their assistance in collecting and the processing of tissues. The authors acknowledge and extend gratitude to Yuan Yuan Ling (retired, formerly of The Scripps Research Institute) for years of service to science. This work was supported by Grants from the U.S. National Institutes of Health (NIH) National Institute on Aging (AG024827, AG044376), NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR051456), and a program grant from the Juvenile Diabetes Research Foundation to P.D.R. R.R.F. was supported by a T32 grant from NIH on Autoimmunity and Immunopathology. This project used the University of Pittsburgh Cancer Institute Vector Facilities (Pittsburgh, PA, USA) supported by the University of Pittsburgh's NIH Cancer Center Support Grant P30 CA047904. The authors declare no conflicts of interest. Publisher Copyright: © FASEB

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Previously, we demonstrated that intratumoral delivery of adenoviral vector encoding single-chain (sc) IL-23 (Ad.scIL-23) was able to induce systemic antitumor immunity. Here, we examined the role of IL-23 in diabetes in nonobese diabetic mice. Intravenous delivery of Ad.scIL-23 did not accelerate the onset of hyperglycemia but instead resulted in the development of psoriatic arthritis. Ad.scIL-23–treated mice developed erythema, scales, and thickening of the skin, as well as intervertebral disc degeneration and extensive synovial hypertrophy and loss of articular cartilage in the knees. Immunological analysis revealed activation of conventional T helper type 17 cells and IL-17–producing γδ T cells along with a significant depletion and suppression of T cells in the pancreatic lymph nodes. Furthermore, treatment with anti–IL-17 antibody reduced joint and skin psoriatic arthritis pathologies. Thus, these Ad.scIL-23–treated mice represent a physiologically relevant model of psoriatic arthritis for understanding disease progression and for testing therapeutic approaches.—Flores, R. R., Carbo, L., Kim, E., Van Meter, M., De Padilla, C. M. L., Zhao, J., Colangelo, D., Yousefzadeh, M. J., Angelini, L. A., Zhang, L., Pola, E., Vo, N., Evans, C. H., Gambotto, A., Niedernhofer, L. J., Robbins, P. D. Adenoviral gene transfer of a single-chain IL-23 induces psoriatic arthritis–like symptoms in NOD mice. FASEB J. 33, 9505–9515 (2019). www.fasebj.org.

AB - Previously, we demonstrated that intratumoral delivery of adenoviral vector encoding single-chain (sc) IL-23 (Ad.scIL-23) was able to induce systemic antitumor immunity. Here, we examined the role of IL-23 in diabetes in nonobese diabetic mice. Intravenous delivery of Ad.scIL-23 did not accelerate the onset of hyperglycemia but instead resulted in the development of psoriatic arthritis. Ad.scIL-23–treated mice developed erythema, scales, and thickening of the skin, as well as intervertebral disc degeneration and extensive synovial hypertrophy and loss of articular cartilage in the knees. Immunological analysis revealed activation of conventional T helper type 17 cells and IL-17–producing γδ T cells along with a significant depletion and suppression of T cells in the pancreatic lymph nodes. Furthermore, treatment with anti–IL-17 antibody reduced joint and skin psoriatic arthritis pathologies. Thus, these Ad.scIL-23–treated mice represent a physiologically relevant model of psoriatic arthritis for understanding disease progression and for testing therapeutic approaches.—Flores, R. R., Carbo, L., Kim, E., Van Meter, M., De Padilla, C. M. L., Zhao, J., Colangelo, D., Yousefzadeh, M. J., Angelini, L. A., Zhang, L., Pola, E., Vo, N., Evans, C. H., Gambotto, A., Niedernhofer, L. J., Robbins, P. D. Adenoviral gene transfer of a single-chain IL-23 induces psoriatic arthritis–like symptoms in NOD mice. FASEB J. 33, 9505–9515 (2019). www.fasebj.org.

KW - adenovirus

KW - interleukin-17

KW - interleukin-23

KW - psoriasis

KW - type 1 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85070787567&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070787567&partnerID=8YFLogxK

U2 - 10.1096/fj.201900420R

DO - 10.1096/fj.201900420R

M3 - Article

C2 - 31170010

AN - SCOPUS:85070787567

SN - 0892-6638

VL - 33

SP - 9505

EP - 9515

JO - FASEB Journal

JF - FASEB Journal

IS - 8

ER -

Adenoviral gene transfer of a single-chain IL-23 induces psoriatic arthritis–like symptoms in NOD mice

Abstract

Bibliographical note

Keywords

UN SDGs

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this