Macrophage-inducible C-type lectin activates B cells to promote T cell reconstitution in heart allograft recipients

Suheyla Hasgur, Yosuke Yamamoto, Ran Fan, Michael Nicosia, Victoria Gorbacheva, Daniel Zwick, Motoo Araki, Robert L. Fairchild, Anna Valujskikh

Research output: Contribution to journalArticlepeer-review

Abstract

Diminishing homeostatic proliferation of memory T cells is essential for improving the efficacy of lymphoablation in transplant recipients. Our previous studies in a mouse heart transplantation model established that B lymphocytes secreting proinflammatory cytokines are critical for T cell recovery after lymphoablation. The goal of the current study was to identify mediators of B cell activation following lymphoablation in allograft recipients. Transcriptome analysis revealed that macrophage-inducible C-type lectin (Mincle, Clec4e) expression is up-regulated in B cells from heart allograft recipients treated with murine anti-thymocyte globulin (mATG). Recipient Mincle deficiency diminishes B cell production of pro-inflammatory cytokines and impairs T lymphocyte reconstitution. Mixed bone marrow chimeras lacking Mincle only in B lymphocytes have similar defects in T cell recovery. Conversely, treatment with a synthetic Mincle ligand enhances T cell reconstitution after lymphoablation in non-transplanted mice. Treatment with agonistic CD40 mAb facilitates T cell reconstitution in CD4 T cell-depleted, but not in Mincle-deficient, recipients indicating that CD40 signaling induces T cell proliferation via a Mincle-dependent pathway. These findings are the first to identify an important function of B cell Mincle as a sensor of damage-associated molecular patterns released by the graft and demonstrate its role in clinically relevant settings of organ transplantation.

Original languageEnglish
JournalAmerican Journal of Transplantation
DOIs
Publication statusAccepted/In press - 2022
Externally publishedYes

Keywords

  • B cell biology
  • basic (laboratory) research/science
  • immunobiology
  • immunosuppressive regimens - induction
  • lymphocyte biology
  • solid organ transplantation
  • T cell biology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Macrophage-inducible C-type lectin activates B cells to promote T cell reconstitution in heart allograft recipients'. Together they form a unique fingerprint.

Cite this