PMID- 35294793 OWN - NLM STAT- MEDLINE DCOM- 20220706 LR - 20230124 IS - 1600-6143 (Electronic) IS - 1600-6135 (Print) IS - 1600-6135 (Linking) VI - 22 IP - 7 DP - 2022 Jul TI - Macrophage-inducible C-type lectin activates B cells to promote T cell reconstitution in heart allograft recipients. PG - 1779-1790 LID - 10.1111/ajt.17033 [doi] AB - 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. CI - (c) 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons. FAU - Hasgur, Suheyla AU - Hasgur S AD - Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Yamamoto, Yosuke AU - Yamamoto Y AD - Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Fan, Ran AU - Fan R AD - Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Nicosia, Michael AU - Nicosia M AD - Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Gorbacheva, Victoria AU - Gorbacheva V AD - Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Zwick, Daniel AU - Zwick D AD - Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Araki, Motoo AU - Araki M AD - Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. FAU - Fairchild, Robert L AU - Fairchild RL AUID- ORCID: 0000-0002-7107-5259 AD - Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Valujskikh, Anna AU - Valujskikh A AUID- ORCID: 0000-0003-3252-0636 AD - Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. LA - eng GR - R01 AI113142/AI/NIAID NIH HHS/United States GR - U01 AI063594/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20220401 PL - United States TA - Am J Transplant JT - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons JID - 100968638 RN - 0 (Cytokines) RN - 0 (Lectins, C-Type) SB - IM MH - Allografts MH - Animals MH - *B-Lymphocytes/metabolism MH - Cytokines/metabolism MH - *Heart Transplantation MH - Lectins, C-Type/metabolism MH - Macrophages MH - Mice MH - Mice, Inbred C57BL PMC - PMC9296143 MID - NIHMS1820892 OTO - NOTNLM OT - B cell biology OT - T cell biology OT - basic (laboratory) research/science OT - immunobiology OT - immunosuppressive regimens - induction OT - lymphocyte biology OT - solid organ transplantation EDAT- 2022/03/17 06:00 MHDA- 2022/07/07 06:00 PMCR- 2022/10/07 CRDT- 2022/03/16 17:18 PHST- 2022/02/21 00:00 [revised] PHST- 2021/11/11 00:00 [received] PHST- 2022/03/12 00:00 [accepted] PHST- 2022/03/17 06:00 [pubmed] PHST- 2022/07/07 06:00 [medline] PHST- 2022/03/16 17:18 [entrez] PHST- 2022/10/07 00:00 [pmc-release] AID - S1600-6135(22)08267-3 [pii] AID - AJT17033 [pii] AID - 10.1111/ajt.17033 [doi] PST - ppublish SO - Am J Transplant. 2022 Jul;22(7):1779-1790. doi: 10.1111/ajt.17033. Epub 2022 Apr 1.