Leucine-rich repeat kinase 2 (Lrrk2) deficiency diminishes the development of experimental autoimmune uveitis (EAU) and the adaptive immune response

Wambui S. Wandu, Cuiyan Tan, Osato Ogbeifun, Barbara P. Vistica, Guangpu Shi, Samuel J H Hinshaw, Chengsong Xie, Xi Chen, Dennis M. Klinman, Huaibin Cai, Igal Gery Gery

Research output: Contribution to journalArticle

Abstract

Background: Mutations in LRRK2 are related to certain forms of Parkinson's disease and, possibly, to the pathogenesis of Crohn's disease. In both these diseases inflammatory processes participate in the pathogenic process. LRRK2 is expressed in lymphoid cells and, interestingly, Lrrk2 (-/-) mice were reported to develop more severe experimental colitis than their wild type (WT) controls. Here, we examined the possible involvement of LRRK2 in the pathogenesis of experimental autoimmune uveitis (EAU), an animal model for human uveitis, by testing Lrrk2 (-/-) mice for their capacity to develop this experimental eye disease and related immune responses. Methods: Lrrk2 (-/-) mice and their WT controls (C57Bl/6) were immunized with interphotoreceptor retinoid-binding protein (IRBP) and compared for their development of EAU, delayed type hypersensitivity (DTH) by skin tests, production of cytokines in culture, and expression of interferon (IFN)-γ, interleukin (IL)-17 and FoxP3 by spleen cells, using flow cytometry. Peritoneal macrophages were examined for their production of cytokines/chemokines in culture following stimulation with LPS or the oligodeoxynucleotide CpG. The Lrrk2 (-/-) and WT mice were also compared for their response to bovine serum albumin (BSA). Results: The Lrrk2 (-/-) mice developed lower levels of EAU, DTH responses and cytokine production by lymphocytes than did their WT controls. Intracellular expression of IFN-γ and IL-17, by spleen cells, and secretion of cytokines/chemokines by activated peritoneal macrophages of Lrrk2 (-/-) mice trended toward diminished levels, although variabilities were noted. The expression levels of FoxP3 by Lrrk2 (-/-) spleen cells, however, were similar to those seen in WT controls. Consistent with their low response to IRBP, Lrrk2 (-/-) mice responded to BSA less vigorously than their WT controls. Conclusions: Lrrk2 deficiency in mice diminished the development of EAU and the related adaptive immune responses to IRBP as compared to the WT controls.

Original languageEnglish (US)
Article numbere0128906
JournalPLoS One
Volume10
Issue number6
DOIs
StatePublished - Jun 11 2015
Externally publishedYes

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Uveitis
Adaptive Immunity
Leucine
leucine
phosphotransferases (kinases)
Phosphotransferases
mice
Cytokines
retinoids
Interleukin-17
Macrophages
cytokines
Bovine Serum Albumin
splenocytes
Spleen
Chemokines
Delayed Hypersensitivity
Peritoneal Macrophages
Interferons
binding proteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Leucine-rich repeat kinase 2 (Lrrk2) deficiency diminishes the development of experimental autoimmune uveitis (EAU) and the adaptive immune response. / Wandu, Wambui S.; Tan, Cuiyan; Ogbeifun, Osato; Vistica, Barbara P.; Shi, Guangpu; Hinshaw, Samuel J H; Xie, Chengsong; Chen, Xi; Klinman, Dennis M.; Cai, Huaibin; Gery, Igal Gery.

In: PLoS One, Vol. 10, No. 6, e0128906, 11.06.2015.

Research output: Contribution to journalArticle

Wandu, WS, Tan, C, Ogbeifun, O, Vistica, BP, Shi, G, Hinshaw, SJH, Xie, C, Chen, X, Klinman, DM, Cai, H & Gery, IG 2015, 'Leucine-rich repeat kinase 2 (Lrrk2) deficiency diminishes the development of experimental autoimmune uveitis (EAU) and the adaptive immune response', PLoS One, vol. 10, no. 6, e0128906. https://doi.org/10.1371/journal.pone.0128906
Wandu, Wambui S. ; Tan, Cuiyan ; Ogbeifun, Osato ; Vistica, Barbara P. ; Shi, Guangpu ; Hinshaw, Samuel J H ; Xie, Chengsong ; Chen, Xi ; Klinman, Dennis M. ; Cai, Huaibin ; Gery, Igal Gery. / Leucine-rich repeat kinase 2 (Lrrk2) deficiency diminishes the development of experimental autoimmune uveitis (EAU) and the adaptive immune response. In: PLoS One. 2015 ; Vol. 10, No. 6.
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abstract = "Background: Mutations in LRRK2 are related to certain forms of Parkinson's disease and, possibly, to the pathogenesis of Crohn's disease. In both these diseases inflammatory processes participate in the pathogenic process. LRRK2 is expressed in lymphoid cells and, interestingly, Lrrk2 (-/-) mice were reported to develop more severe experimental colitis than their wild type (WT) controls. Here, we examined the possible involvement of LRRK2 in the pathogenesis of experimental autoimmune uveitis (EAU), an animal model for human uveitis, by testing Lrrk2 (-/-) mice for their capacity to develop this experimental eye disease and related immune responses. Methods: Lrrk2 (-/-) mice and their WT controls (C57Bl/6) were immunized with interphotoreceptor retinoid-binding protein (IRBP) and compared for their development of EAU, delayed type hypersensitivity (DTH) by skin tests, production of cytokines in culture, and expression of interferon (IFN)-γ, interleukin (IL)-17 and FoxP3 by spleen cells, using flow cytometry. Peritoneal macrophages were examined for their production of cytokines/chemokines in culture following stimulation with LPS or the oligodeoxynucleotide CpG. The Lrrk2 (-/-) and WT mice were also compared for their response to bovine serum albumin (BSA). Results: The Lrrk2 (-/-) mice developed lower levels of EAU, DTH responses and cytokine production by lymphocytes than did their WT controls. Intracellular expression of IFN-γ and IL-17, by spleen cells, and secretion of cytokines/chemokines by activated peritoneal macrophages of Lrrk2 (-/-) mice trended toward diminished levels, although variabilities were noted. The expression levels of FoxP3 by Lrrk2 (-/-) spleen cells, however, were similar to those seen in WT controls. Consistent with their low response to IRBP, Lrrk2 (-/-) mice responded to BSA less vigorously than their WT controls. Conclusions: Lrrk2 deficiency in mice diminished the development of EAU and the related adaptive immune responses to IRBP as compared to the WT controls.",
author = "Wandu, {Wambui S.} and Cuiyan Tan and Osato Ogbeifun and Vistica, {Barbara P.} and Guangpu Shi and Hinshaw, {Samuel J H} and Chengsong Xie and Xi Chen and Klinman, {Dennis M.} and Huaibin Cai and Gery, {Igal Gery}",
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AU - Tan, Cuiyan

AU - Ogbeifun, Osato

AU - Vistica, Barbara P.

AU - Shi, Guangpu

AU - Hinshaw, Samuel J H

AU - Xie, Chengsong

AU - Chen, Xi

AU - Klinman, Dennis M.

AU - Cai, Huaibin

AU - Gery, Igal Gery

PY - 2015/6/11

Y1 - 2015/6/11

N2 - Background: Mutations in LRRK2 are related to certain forms of Parkinson's disease and, possibly, to the pathogenesis of Crohn's disease. In both these diseases inflammatory processes participate in the pathogenic process. LRRK2 is expressed in lymphoid cells and, interestingly, Lrrk2 (-/-) mice were reported to develop more severe experimental colitis than their wild type (WT) controls. Here, we examined the possible involvement of LRRK2 in the pathogenesis of experimental autoimmune uveitis (EAU), an animal model for human uveitis, by testing Lrrk2 (-/-) mice for their capacity to develop this experimental eye disease and related immune responses. Methods: Lrrk2 (-/-) mice and their WT controls (C57Bl/6) were immunized with interphotoreceptor retinoid-binding protein (IRBP) and compared for their development of EAU, delayed type hypersensitivity (DTH) by skin tests, production of cytokines in culture, and expression of interferon (IFN)-γ, interleukin (IL)-17 and FoxP3 by spleen cells, using flow cytometry. Peritoneal macrophages were examined for their production of cytokines/chemokines in culture following stimulation with LPS or the oligodeoxynucleotide CpG. The Lrrk2 (-/-) and WT mice were also compared for their response to bovine serum albumin (BSA). Results: The Lrrk2 (-/-) mice developed lower levels of EAU, DTH responses and cytokine production by lymphocytes than did their WT controls. Intracellular expression of IFN-γ and IL-17, by spleen cells, and secretion of cytokines/chemokines by activated peritoneal macrophages of Lrrk2 (-/-) mice trended toward diminished levels, although variabilities were noted. The expression levels of FoxP3 by Lrrk2 (-/-) spleen cells, however, were similar to those seen in WT controls. Consistent with their low response to IRBP, Lrrk2 (-/-) mice responded to BSA less vigorously than their WT controls. Conclusions: Lrrk2 deficiency in mice diminished the development of EAU and the related adaptive immune responses to IRBP as compared to the WT controls.

AB - Background: Mutations in LRRK2 are related to certain forms of Parkinson's disease and, possibly, to the pathogenesis of Crohn's disease. In both these diseases inflammatory processes participate in the pathogenic process. LRRK2 is expressed in lymphoid cells and, interestingly, Lrrk2 (-/-) mice were reported to develop more severe experimental colitis than their wild type (WT) controls. Here, we examined the possible involvement of LRRK2 in the pathogenesis of experimental autoimmune uveitis (EAU), an animal model for human uveitis, by testing Lrrk2 (-/-) mice for their capacity to develop this experimental eye disease and related immune responses. Methods: Lrrk2 (-/-) mice and their WT controls (C57Bl/6) were immunized with interphotoreceptor retinoid-binding protein (IRBP) and compared for their development of EAU, delayed type hypersensitivity (DTH) by skin tests, production of cytokines in culture, and expression of interferon (IFN)-γ, interleukin (IL)-17 and FoxP3 by spleen cells, using flow cytometry. Peritoneal macrophages were examined for their production of cytokines/chemokines in culture following stimulation with LPS or the oligodeoxynucleotide CpG. The Lrrk2 (-/-) and WT mice were also compared for their response to bovine serum albumin (BSA). Results: The Lrrk2 (-/-) mice developed lower levels of EAU, DTH responses and cytokine production by lymphocytes than did their WT controls. Intracellular expression of IFN-γ and IL-17, by spleen cells, and secretion of cytokines/chemokines by activated peritoneal macrophages of Lrrk2 (-/-) mice trended toward diminished levels, although variabilities were noted. The expression levels of FoxP3 by Lrrk2 (-/-) spleen cells, however, were similar to those seen in WT controls. Consistent with their low response to IRBP, Lrrk2 (-/-) mice responded to BSA less vigorously than their WT controls. Conclusions: Lrrk2 deficiency in mice diminished the development of EAU and the related adaptive immune responses to IRBP as compared to the WT controls.

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