Clr-f expression regulates kidney immune and metabolic homeostasis

Haggag S. Zein; Elias Abou-Samra; Michal Scur; Alex Gutsol; Clayton W. Hall; Bishal Dasgupta; Lara Gharibeh; Turki Abujamel; Daniel Medina-Luna; Gayani S. Gamage; Tessa J. Pelino; Mona Nemer; Mir Munir A. Rahim; Alexander Steinle; Brendon D. Parsons; Andrew P. Makrigiannis

doi:10.1038/s41598-022-08547-9

Clr-f expression regulates kidney immune and metabolic homeostasis

Haggag S. Zein, Elias Abou-Samra, Michal Scur, Alex Gutsol, Clayton W. Hall, Bishal Dasgupta, Lara Gharibeh, Turki Abujamel, Daniel Medina-Luna, Gayani S. Gamage, Tessa J. Pelino, Mona Nemer, Mir Munir A. Rahim, Alexander Steinle, Brendon D. Parsons, Andrew P. Makrigiannis

Medicine

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

4 Citas (Scopus)

Resumen

The C-type lectin-related protein, Clr-f, encoded by Clec2h in the mouse NK gene complex (NKC), is a member of a family of immune regulatory lectins that guide immune responses at distinct tissues of the body. Clr-f is highly expressed in the kidney; however, its activity in this organ is unknown. To assess the requirement for Clr-f in kidney health and function, we generated a Clr-f-deficient mouse (Clr-f^−/−) by targeted deletions in the Clec2h gene. Mice lacking Clr-f exhibited glomerular and tubular lesions, immunoglobulin and C3 complement protein renal deposits, and significant abdominal and ectopic lipid accumulation. Whole kidney transcriptional profile analysis of Clr-f^−/− mice at 7, 13, and 24 weeks of age revealed a dynamic dysregulation in lipid metabolic processes, stress responses, and inflammatory mediators. Examination of the immune contribution to the pathologies of Clr-f^−/− mouse kidneys identified elevated IL-12 and IFNγ in cells of the tubulointerstitium, and an infiltrating population of neutrophils and T and B lymphocytes. The presence of these insults in a Rag1^−/−Clr-f^−/− background reveals that Clr-f^−/− mice are susceptible to a T and B lymphocyte-independent renal pathogenesis. Our data reveal a role for Clr-f in the maintenance of kidney immune and metabolic homeostasis.

Idioma original	English
Número de artículo	4834
Publicación	Scientific Reports
Volumen	12
N.º	1
DOI	https://doi.org/10.1038/s41598-022-08547-9
Estado	Published - dic. 2022

Nota bibliográfica

Funding Information:
We thank the Dalhousie University CORES for flow cytometry and microscopy support. This work was supported by the Kidney Foundation of Canada (KFOC190027) to APM. DML is a trainee in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute, with funds provided by the DMRF Jean Rivers Sawyer Award and the GIVETOLIVE Eric Douglas Grant Award.

Funding Information:
We thank the Dalhousie University CORES for flow cytometry and microscopy support. This work was supported by the Kidney Foundation of Canada (KFOC190027) to APM. DML is a trainee in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute, with funds provided by the DMRF Jean Rivers Sawyer Award and the GIVETOLIVE Eric Douglas Grant Award.

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus Subject Areas

General

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

Acceder al documento

10.1038/s41598-022-08547-9

Otros archivos y enlaces

Citar esto

Zein, H. S., Abou-Samra, E., Scur, M., Gutsol, A., Hall, C. W., Dasgupta, B., Gharibeh, L., Abujamel, T., Medina-Luna, D., Gamage, G. S., Pelino, T. J., Nemer, M., Rahim, M. M. A., Steinle, A., Parsons, B. D., & Makrigiannis, A. P. (2022). Clr-f expression regulates kidney immune and metabolic homeostasis. Scientific Reports, 12(1), Artículo 4834. https://doi.org/10.1038/s41598-022-08547-9

@article{4374f5b627064911a2b7c54e759dc561,

title = "Clr-f expression regulates kidney immune and metabolic homeostasis",

abstract = "The C-type lectin-related protein, Clr-f, encoded by Clec2h in the mouse NK gene complex (NKC), is a member of a family of immune regulatory lectins that guide immune responses at distinct tissues of the body. Clr-f is highly expressed in the kidney; however, its activity in this organ is unknown. To assess the requirement for Clr-f in kidney health and function, we generated a Clr-f-deficient mouse (Clr-f−/−) by targeted deletions in the Clec2h gene. Mice lacking Clr-f exhibited glomerular and tubular lesions, immunoglobulin and C3 complement protein renal deposits, and significant abdominal and ectopic lipid accumulation. Whole kidney transcriptional profile analysis of Clr-f−/− mice at 7, 13, and 24 weeks of age revealed a dynamic dysregulation in lipid metabolic processes, stress responses, and inflammatory mediators. Examination of the immune contribution to the pathologies of Clr-f−/− mouse kidneys identified elevated IL-12 and IFNγ in cells of the tubulointerstitium, and an infiltrating population of neutrophils and T and B lymphocytes. The presence of these insults in a Rag1−/−Clr-f−/− background reveals that Clr-f−/− mice are susceptible to a T and B lymphocyte-independent renal pathogenesis. Our data reveal a role for Clr-f in the maintenance of kidney immune and metabolic homeostasis.",

author = "Zein, {Haggag S.} and Elias Abou-Samra and Michal Scur and Alex Gutsol and Hall, {Clayton W.} and Bishal Dasgupta and Lara Gharibeh and Turki Abujamel and Daniel Medina-Luna and Gamage, {Gayani S.} and Pelino, {Tessa J.} and Mona Nemer and Rahim, {Mir Munir A.} and Alexander Steinle and Parsons, {Brendon D.} and Makrigiannis, {Andrew P.}",

note = "Funding Information: We thank the Dalhousie University CORES for flow cytometry and microscopy support. This work was supported by the Kidney Foundation of Canada (KFOC190027) to APM. DML is a trainee in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute, with funds provided by the DMRF Jean Rivers Sawyer Award and the GIVETOLIVE Eric Douglas Grant Award. Funding Information: We thank the Dalhousie University CORES for flow cytometry and microscopy support. This work was supported by the Kidney Foundation of Canada (KFOC190027) to APM. DML is a trainee in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute, with funds provided by the DMRF Jean Rivers Sawyer Award and the GIVETOLIVE Eric Douglas Grant Award. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41598-022-08547-9",

language = "English",

volume = "12",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Clr-f expression regulates kidney immune and metabolic homeostasis

AU - Zein, Haggag S.

AU - Abou-Samra, Elias

AU - Scur, Michal

AU - Gutsol, Alex

AU - Hall, Clayton W.

AU - Dasgupta, Bishal

AU - Gharibeh, Lara

AU - Abujamel, Turki

AU - Medina-Luna, Daniel

AU - Gamage, Gayani S.

AU - Pelino, Tessa J.

AU - Nemer, Mona

AU - Rahim, Mir Munir A.

AU - Steinle, Alexander

AU - Parsons, Brendon D.

AU - Makrigiannis, Andrew P.

N1 - Funding Information: We thank the Dalhousie University CORES for flow cytometry and microscopy support. This work was supported by the Kidney Foundation of Canada (KFOC190027) to APM. DML is a trainee in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute, with funds provided by the DMRF Jean Rivers Sawyer Award and the GIVETOLIVE Eric Douglas Grant Award. Funding Information: We thank the Dalhousie University CORES for flow cytometry and microscopy support. This work was supported by the Kidney Foundation of Canada (KFOC190027) to APM. DML is a trainee in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute, with funds provided by the DMRF Jean Rivers Sawyer Award and the GIVETOLIVE Eric Douglas Grant Award. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - The C-type lectin-related protein, Clr-f, encoded by Clec2h in the mouse NK gene complex (NKC), is a member of a family of immune regulatory lectins that guide immune responses at distinct tissues of the body. Clr-f is highly expressed in the kidney; however, its activity in this organ is unknown. To assess the requirement for Clr-f in kidney health and function, we generated a Clr-f-deficient mouse (Clr-f−/−) by targeted deletions in the Clec2h gene. Mice lacking Clr-f exhibited glomerular and tubular lesions, immunoglobulin and C3 complement protein renal deposits, and significant abdominal and ectopic lipid accumulation. Whole kidney transcriptional profile analysis of Clr-f−/− mice at 7, 13, and 24 weeks of age revealed a dynamic dysregulation in lipid metabolic processes, stress responses, and inflammatory mediators. Examination of the immune contribution to the pathologies of Clr-f−/− mouse kidneys identified elevated IL-12 and IFNγ in cells of the tubulointerstitium, and an infiltrating population of neutrophils and T and B lymphocytes. The presence of these insults in a Rag1−/−Clr-f−/− background reveals that Clr-f−/− mice are susceptible to a T and B lymphocyte-independent renal pathogenesis. Our data reveal a role for Clr-f in the maintenance of kidney immune and metabolic homeostasis.

AB - The C-type lectin-related protein, Clr-f, encoded by Clec2h in the mouse NK gene complex (NKC), is a member of a family of immune regulatory lectins that guide immune responses at distinct tissues of the body. Clr-f is highly expressed in the kidney; however, its activity in this organ is unknown. To assess the requirement for Clr-f in kidney health and function, we generated a Clr-f-deficient mouse (Clr-f−/−) by targeted deletions in the Clec2h gene. Mice lacking Clr-f exhibited glomerular and tubular lesions, immunoglobulin and C3 complement protein renal deposits, and significant abdominal and ectopic lipid accumulation. Whole kidney transcriptional profile analysis of Clr-f−/− mice at 7, 13, and 24 weeks of age revealed a dynamic dysregulation in lipid metabolic processes, stress responses, and inflammatory mediators. Examination of the immune contribution to the pathologies of Clr-f−/− mouse kidneys identified elevated IL-12 and IFNγ in cells of the tubulointerstitium, and an infiltrating population of neutrophils and T and B lymphocytes. The presence of these insults in a Rag1−/−Clr-f−/− background reveals that Clr-f−/− mice are susceptible to a T and B lymphocyte-independent renal pathogenesis. Our data reveal a role for Clr-f in the maintenance of kidney immune and metabolic homeostasis.

UR - http://www.scopus.com/inward/record.url?scp=85126805012&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85126805012&partnerID=8YFLogxK

U2 - 10.1038/s41598-022-08547-9

DO - 10.1038/s41598-022-08547-9

M3 - Article

C2 - 35318366

AN - SCOPUS:85126805012

SN - 2045-2322

VL - 12

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 4834

ER -

Clr-f expression regulates kidney immune and metabolic homeostasis

Resumen

Nota bibliográfica

ASJC Scopus Subject Areas

PubMed: MeSH publication types

Acceder al documento

Otros archivos y enlaces

Huella

Citar esto