Date: Saturday, May 30, 2020
Session Name: Innate Immunity; Chemokines, Cytokines, Complement
Session Time: 3:15pm-4:45pm
Presentation Time: 3:27pm-3:39pm
*Purpose: We have recently demonstrated that co-stimulatory blockade (CSB)-induced mouse lung allograft acceptance depends on a rapid influx of eosinophils that function to downregulate T cell immune responses. However, the mechanisms of CSB-mediated eosinophil migration is unknown.
*Methods: Balb/c (H2d) to C57BL6 (H2b) left single lung transplants were performed as previously described in the presence or absence of CSB immunosuppression through a one-time perioperative administration of anti-CD154 (clone MR1) and anti-CD80/86 blockade (CTLA4Ig). Lung grafts were harvested at either day 4 or day 7 and evaluated for chemokine and cytokine profile as well as influx of eosinophils.
*Results: Higher numbers of eosinophils were evident in CSB-treated compared to control grafts without immunosuppression (Figure 1a). These increased numbers were the result of increased eosinophil homing and retention (Figure 1b). Quantitative PCR of the lung grafts demonstrated upregulation of IL-5 but not eotaxin-1 (CCL11) or eotaxin-2(CCL24) (Figure 2). Flow cytometric analysis confirmed higher numbers of IL-5 producing cells in CSB-treated lungs which had a Lineage–CD90+IL33R+CD25+ phenotype consistent with type 2 innate lymphoid cells (ILC2) (Figure 3).
*Conclusions: The role of ILCs in lung allograft homeostasis is unknown. We now demonstrate that ILC2s play a critical role in lung allograft acceptance by facilitating recruitment of eosinophils through production of IL-5. Our data suggests that modulation of local innate lymphoid cells may present a viable strategy for tolerance induction in the lung.
To cite this abstract in AMA style:Guo Y, Mei Z, Hata A, Mahgoub B, Li D, Manafi A, Banerjee A, Gelman A, Kreisel D, Krupnick A. Co-Stimulatory Blockade Immunosuppression Facilitates Lung Allograft Acceptance Through an Increase in Local IL-5 Production by Type 2 Innate Lymphoid Cells [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/co-stimulatory-blockade-immunosuppression-facilitates-lung-allograft-acceptance-through-an-increase-in-local-il-5-production-by-type-2-innate-lymphoid-cells/. Accessed March 8, 2021.
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