Involvement of M1-Activated Macrophages and Perforin/Granulysin Expressing Lymphocytes in IgA Vasculitis Nephritis

Int J Mol Sci. 2024 Feb 13;25(4):2253. doi: 10.3390/ijms25042253.

Abstract

We investigated the polarisation of CD68+ macrophages and perforin and granulysin distributions in kidney lymphocyte subsets of children with IgA vasculitis nephritis (IgAVN). Pro-inflammatory macrophage (M)1 (CD68/iNOS) or regulatory M2 (CD68/arginase-1) polarisation; spatial arrangement of macrophages and lymphocytes; and perforin and granulysin distribution in CD3+ and CD56+ cells were visulaised using double-labelled immunofluorescence. In contrast to the tubules, iNOS+ cells were more abundant than the arginase-1+ cells in the glomeruli. CD68+ macrophage numbers fluctuated in the glomeruli and were mostly labelled with iNOS. CD68+/arginase-1+ cells are abundant in the tubules. CD56+ cells, enclosed by CD68+ cells, were more abundant in the glomeruli than in the tubuli, and co-expressed NKp44. The glomerular and interstitial/intratubular CD56+ cells express perforin and granulysin, respectively. The CD3+ cells did not express perforin, while a minority expressed granulysin. Innate immunity, represented by M1 macrophages and CD56+ cells rich in perforin and granulysin, plays a pivotal role in the acute phase of IgAVN.

Keywords: Henoch–Schönlein purpura nephritis; IgA vasculitis nephritis; NK cells; T cells; granulysin; macrophage polarisation; perforin.

MeSH terms

  • Adolescent
  • Antigens, Differentiation, T-Lymphocyte* / metabolism
  • Arginase / metabolism
  • Child
  • Female
  • Humans
  • IgA Vasculitis* / complications
  • Killer Cells, Natural* / immunology
  • Macrophage Activation*
  • Macrophages* / immunology
  • Male
  • Nephritis* / immunology
  • Perforin* / metabolism

Substances

  • Arginase
  • Perforin
  • GNLY protein, human
  • Antigens, Differentiation, T-Lymphocyte