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

Producción científica: Contribución a una revistaArtículorevisión 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 originalEnglish
Número de artículo4834
PublicaciónScientific Reports
Volumen12
N.º1
DOI
EstadoPublished - 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

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