In modern transplant and biomedicine, a proper understanding of both allo-and auto-immune processes is of key importance to minimize acute and chronic graft failure and consecutive rejection / pathology through both cellular and humoral effector mechanisms (Figure 1), e.g. cellular and humoral allo-sensitization, alloantigen-reactive T and B cells with the latter producing donor-specific anti-human leukocyte antigen (HLA) alloantibodies (DSA), but also the contribution of autoantibodies [1][2][3][4][5][6][7] . This field includes many diverse disciplines, but similar underlying principles, such as the need for HLA-matching of donor organs /stem cells and recipient, prevention and treatment of graft-versus-host disease (GvHD) 7 , and the common need for effective immunosuppression (e.g. steroids or tacrolimus, TAC/FK506) 8 , as standard immunosuppressive agent for life-long therapy.Transplantation of donor-tissues, -organs, and vascularized composite allografts, is commonly summarized under the term solid organ transplantation (SOT), including e.g. hand, kidney, liver, heart, lung, and intestinal transplantation 8,9 . Of similar importance is hematopoietic stem cell transplantation (HSCT), to reconstitute the stem and progenitor cell compartment in the bone marrow, with both SOT and HSCT entailing GvHD as potential complication 7,10 . In addition, there are numerous novel approaches of cell and gene therapies (CGTs), including advanced therapy medicinal products (ATMPs), in the US and Europe, respectively [10][11][12][13][14] .Adjunct technology, such as machine perfusion of donor organs (e.g. hypo-vs. normothermic) and kidney / renal replacement therapies (RRTs) comprise another promising new field [15][16][17][18] .
Khorki and Shi et al. from Cincinnati Children's Hospital Medical Center in Ohio, USA, contributed the article: "Prior viral infection primes cross-reactive CD8+ T cells that respond to mouse hear allografts.". The authors studied the connection between transplant rejection and presence of high levels of pre-existing memory T cells, in particular virus-specific memory T cells that can drive allograft rejection in allo-MHC animal models and clinical transplantation 1-3, 19-26 . They established a mouse model that can track virus-specific, allo-specific, and crossreactive T cells, revealing that prior infection induces substantial numbers of virus-specific T cells that cross-react to alloantigen, manifesting as early acute rejection of the heart allograft.
Pittsburgh, USA) with Vijay Gorantla (Wake Forest Institute of Regenerative Medicine, USA) contributed the article: "Peripheral nerve repair is associated with augmented cross-tissue inflammation following vascularized composite allotransplantation (VCA).". Indeed, VCA with concomitant nerve repair / coadaption (NR) and adjunct TAC immunosuppressive therapy is used to repair traumatic injuries, but often complicated by innate and adaptive immune activation / inflammation spanning multiple tissues 27 . The effect of NR on the inflammatory cascade is currently unknown [28][29][30] , while TAC has been reported to enhance NR [31][32][33] . The authors here found, that while NR is considered necessary for graft function, it may result in dysregulated and mis-compartmentalized inflammation post VCA and thus suitable mitigation strategies are needed, pointing at their spatiotemporal bioinformatics pipeline.
Organ Transplantation at the Tianjin First Central Hospital in China, contributed the article: "Hypothermic machine perfusion alleviates ischemia-reperfusion injury (IRI) of intestinal transplantation (IT) in pigs.". IT is vulnerable to IRI, and due to the limitations of static cold storage (SCS), hypothermic machine perfusion (HMP) is rapidly gaining in popularity [34][35][36][37][38][39][40] .Here, the authors established a stable intestinal HMP system and demonstrated that HMP could significantly alleviate intestinal IRI and improve the respective outcome after IT in pigs.
Wang et al. from the Department of General Surgery in Lanzhou China, contributed the article: "Fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS): a systematic review and meta-analysis of randomized controlled trials (RCTs).". The authors here assessed the safety and efficacy of FMT for patients with IBS in 19 RCTs withing their PROSPERO study (CRD42022328377; https://www.crd.york.ac.uk/prospero/). They found that a single stool FMT was effective and safe for patients with IBS. At 3-36 months post initiation of treatment, FMT could significantly reduce the IBS-SSS score and improve the clinical response rate. However, the authors did not find a positive effect of capsule FMT on patients with IBS. an essential role in many biological processes and exerts deacetylation-dependent and independent effects on a variety of molecular targets, including modulation of both innate and adaptive immune pathways 41 . The authors here reason that HDAC6 inhibitors may be promising therapeutic candidates in kidney transplantation, e.g. to counteract ischemia reperfusion injury (IRI), to induced immune tolerance, to protect against oxidative stress, and to attenuate chronic interstitial fibrosis of the transplanted kidneys [42][43][44][45] . with a minor but significant contribution from non-HLA-directed auto-antigen-specific autoantibodies (e.g. GPCR-directed regulatory autoantibodies, RABs). Abbreviations: APC, antigen-presenting cell; ATMP, advanced therapy medicinal product; CGT, cell and gene therapy; MHC, major histocompatibility complex; HLA, human leukocyte antigen; HSCT, hematopoietic stem cell transplantation; SOT, solid organ transplantation; Teff and Treg, effector and regulatory T cells; GPCR, G-protein coupled receptor; RAB, regulatory autoantibodies of non-HLA type that are e.g. GPCR-directed, as distinguished from anti-HLAdirected alloantibodies and donor-specific alloantibodies (DSA).
