Limits...
Leucine-Rich Repeat Kinase 2 (Lrrk2) Deficiency Diminishes the Development of Experimental Autoimmune Uveitis (EAU) and the Adaptive Immune Response.

Wandu WS, Tan C, Ogbeifun O, Vistica BP, Shi G, Hinshaw SJ, Xie C, Chen X, Klinman DM, Cai H, Gery I - PLoS ONE (2015)

Bottom Line: In both these diseases inflammatory processes participate in the pathogenic process.Peritoneal macrophages were examined for their production of cytokines/chemokines in culture following stimulation with LPS or the oligodeoxynucleotide CpG.The expression levels of FoxP3 by Lrrk2 (-/-) spleen cells, however, were similar to those seen in WT controls.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus

Similar levels of Treg cells expressing FoxP3 in spleens of Lrrk2 (-/-) (“KO”) and their WT controls.Spleens from mice of the two groups were collected 14 days post immunization, pooled, and their cells were examined by flow cytometry for expression of FoxP3. A. A representative experiment. B. Mean +/- SEM of proportions of FoxP3 cells in spleens of mice of the two groups from five individual experiments.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4465928&req=5

pone.0128906.g004: Similar levels of Treg cells expressing FoxP3 in spleens of Lrrk2 (-/-) (“KO”) and their WT controls.Spleens from mice of the two groups were collected 14 days post immunization, pooled, and their cells were examined by flow cytometry for expression of FoxP3. A. A representative experiment. B. Mean +/- SEM of proportions of FoxP3 cells in spleens of mice of the two groups from five individual experiments.

Mentions: To examine the possibility that the inferior immune responsiveness in Lrrk2 (-/-) mice is due to increased levels of Treg cells, we compared by flow cytometry the proportions of CD4 cells expressing FoxP3 in spleens of the two mouse groups. FoxP3 is a transcription factor specifically expressed by Treg cells [20, 21]. Fig 4A shows the flow cytometric data of a representative experiment and the data of this and four other experiments are summarized in Fig 4B. Just minute differences were noted between the Lrrk2 (-/-) and their WT controls in the proportions of FoxP3 expressing cells in their spleen, indicating that the lower immune response in the Lrrk2 (-/-) mice is not due to increase in proportions of Treg cells.


Leucine-Rich Repeat Kinase 2 (Lrrk2) Deficiency Diminishes the Development of Experimental Autoimmune Uveitis (EAU) and the Adaptive Immune Response.

Wandu WS, Tan C, Ogbeifun O, Vistica BP, Shi G, Hinshaw SJ, Xie C, Chen X, Klinman DM, Cai H, Gery I - PLoS ONE (2015)

Similar levels of Treg cells expressing FoxP3 in spleens of Lrrk2 (-/-) (“KO”) and their WT controls.Spleens from mice of the two groups were collected 14 days post immunization, pooled, and their cells were examined by flow cytometry for expression of FoxP3. A. A representative experiment. B. Mean +/- SEM of proportions of FoxP3 cells in spleens of mice of the two groups from five individual experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4465928&req=5

pone.0128906.g004: Similar levels of Treg cells expressing FoxP3 in spleens of Lrrk2 (-/-) (“KO”) and their WT controls.Spleens from mice of the two groups were collected 14 days post immunization, pooled, and their cells were examined by flow cytometry for expression of FoxP3. A. A representative experiment. B. Mean +/- SEM of proportions of FoxP3 cells in spleens of mice of the two groups from five individual experiments.
Mentions: To examine the possibility that the inferior immune responsiveness in Lrrk2 (-/-) mice is due to increased levels of Treg cells, we compared by flow cytometry the proportions of CD4 cells expressing FoxP3 in spleens of the two mouse groups. FoxP3 is a transcription factor specifically expressed by Treg cells [20, 21]. Fig 4A shows the flow cytometric data of a representative experiment and the data of this and four other experiments are summarized in Fig 4B. Just minute differences were noted between the Lrrk2 (-/-) and their WT controls in the proportions of FoxP3 expressing cells in their spleen, indicating that the lower immune response in the Lrrk2 (-/-) mice is not due to increase in proportions of Treg cells.

Bottom Line: In both these diseases inflammatory processes participate in the pathogenic process.Peritoneal macrophages were examined for their production of cytokines/chemokines in culture following stimulation with LPS or the oligodeoxynucleotide CpG.The expression levels of FoxP3 by Lrrk2 (-/-) spleen cells, however, were similar to those seen in WT controls.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus