The Dual Regulatory Roles of Macrophages in Acute Allogeneic Organ Graft Rejection

Innate immune cells are critical for transplant response.As an important cellular component of innate immune cells,macrophages are the predominate infiltrated cells in allografts,and macrophage accumulation in allografts is negatively associated with the short-and long-term outcomes of organ transplantation.Macrophages are functionally heterogeneous and plastic.They participate in organ graft rejection through multiple pathways,including antigen presentation,the expression of costimulatory molecules and cytokines,and direct cytotoxicity and injury ability to allografts.However,some macrophage subpopulations,such as regulatory macrophages,can protect allografts from immune rejection and promote transplant immune tolerance with their immune regulatory properties.Although researchers recognize the potential roles macrophages play in allograft injury,they pay insufficient attention to the diverse roles of macrophages in allograft rejection.We herein briefly summarize the distinctive roles of macrophages in acute transplant immune response and the effect of immunosuppressive drugs on macrophages.Greater attention should be paid to the complex and critical function of macrophages in allograft rejection,and more effort should be put into developing immunosuppressive drugs that specifically target macrophages,which would ultimately improve the long-term survival of organ grafts in patients.

Two kinds of macrophage memory:innate and adaptive immune-like macrophage memory

It is believed that the adaptive immune system responds to nonself entities with its specificity and memory properties.In contrast,the innate immune system lacks adaptive characteristics.Whether innate immune cells can generate adaptive immune features has always been an unanswered question.

Towards Personalized Intervention for Alzheimer's Disease

Alzheimer＇s disease （AD） remains to be a grand challenge for the international community despite over a century of exploration. A key factor likely accounting for such a situation is the vast heterogeneity in the disease etiology, which involves very complex and divergent pathways. Therefore, intervention strategies shall be tailored for subgroups of AD patients. Both demographic and in-depth information is needed for patient stratification. The demographic information includes primarily APOE genotype, age, gender, education, environmental exposure, life style, and medical history, whereas in-depth information stems from genome sequencing, brain imaging, peripheral biomarkers, and even functional assays on neurons derived from patient-specific induced pluripotent cells （iPSCs）. Comprehensive information collection, better understanding of the disease mech- anisms, and diversified strategies of drug development would help with more effective intervention in the foreseeable future.

Defining newly formed and tissue-resident bone marrow-derived macrophages in adult mice based on lysozyme expression

Tissue-resident macrophages are derived from different precursor cells and display different phenotypes.Reconstitution of the tissue-resident macrophages of inflamed or damaged tissues in adults can be achieved by bone marrow-derived monocytes/macrophages.Using lysozyme(Lysm)-GFP-reporter mice,we found that alveolar macrophages(AMs),Kupffer cells,red pulp macrophages(RpMacs),and kidney-resident macrophages were Lysm-GFP^(−),whereas all monocytes in the fetal liver,adult bone marrow,and blood were Lysm-GFP^(+).Donor-derived Lysm-GFP^(+)resident macrophages gradually became Lysm-GFP−in recipients and developed gene expression profiles characteristic of tissue-resident macrophages.Thus,Lysm may be used to distinguish newly formed and long-term surviving tissue-resident macrophages that were derived from bone marrow precursor cells in adult mice under pathological conditions.Furthermore,we found that Irf4 might be essential for resident macrophage differentiation in all tissues,while cytokine and receptor pathways,mTOR signaling pathways,and fatty acid metabolic processes predominantly regulated the differentiation of RpMacs,Kupffer cells,and kidney macrophages,respectively.Deficiencies in ST2,mechanistic target of rapamycin(mTOR)and fatty acid-binding protein 5(FABP5)differentially impaired the differentiation of tissue-resident macrophages from bone marrow-derived monocytes/macrophages in the lungs,liver,and kidneys.These results indicate that a combination of shared and unique signaling pathways coordinately shape tissue-resident macrophage differentiation in various tissues.