Eosinophils promote inducible NOS–mediated lung allograft acceptance

Onyema, Oscar Okwudiri; Guo, Yanxia; Wang, Qing; Stoler, Mark H.; Lau, Christine L.; Li, Kang; Nazaroff, Christopher D.; Wang, Xingan; Li, Wenjun; Kreisel, Daniel; Gelman, Andrew E.; Lee, James J.; Jacobsen, Elizabeth A.; Krupnick, Alexander S.

doi:10.1172/jci.insight.96455

Cited by 25 publications

(50 citation statements)

References 44 publications

(56 reference statements)

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“…Interestingly, eosinophil depletion did not ameliorate rejection but actually prevented co‐stimulatory blockade (CSB)‐mediated graft acceptance and accentuated rejection in the absence of immunosuppression (Figure ). Unlike previous reports, which demonstrated an association of Th2 cytokines with the tolerance, we demonstrated that both CSB‐treated accepting as well nonimmunosuppressed rejecting grafts demonstrate a Th1 polarized microenvironment . This was marked by increased expression of IFN‐γ and TNF‐α without significant impact on Th2‐associated cytokines such as IL‐4, GM‐CSF, and IL‐33 .…”

Section: Eosinophils In Lung Transplantationcontrasting

confidence: 88%

“…Our observation supports the unique role of pro‐inflammatory mediators in promoting lung allograft tolerance and reaffirms the uniqueness of lung‐specific immune responses . In line with Th1 polarization of the lung allograft microenvironment, eosinophils from both accepting and rejecting lung grafts were polarized to a Th1 (or E1)‐like phenotype . The Th1 signature of the lung allograft eosinophil differs from the Th2 (or E2)‐type associated with asthma and allergic inflammation …”

Section: Eosinophils In Lung Transplantationsupporting

confidence: 81%

“…Indeed, Th1 polarization was a key component to eosinophil regulatory capacity because amelioration of the Th1 phenotype blocked eosinophil‐mediated suppression . Interestingly, we and others have previously described the expression of iNOS to be a key component of lung‐specific immunoregulation . Th1 polarization was characterized by upregulation of iNOS in lung‐resident eosinophils.…”

Section: Eosinophils In Lung Transplantationmentioning

confidence: 95%

“…In order to establish clarity regarding the role of eosinophils in lung allograft homeostasis, we utilized a clinically relevant murine model of left lung transplantation . We initially depleted eosinophils from lung graft recipients through either neutralization of IL‐5 or targeted deletion in transgenic mice, where the diphtheria toxin receptor is expressed under the control of eosinophil peroxidase promoter (iPHIL mice) . Interestingly, eosinophil depletion did not ameliorate rejection but actually prevented co‐stimulatory blockade (CSB)‐mediated graft acceptance and accentuated rejection in the absence of immunosuppression (Figure ).…”

Section: Eosinophils In Lung Transplantationmentioning

confidence: 99%

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Deciphering the role of eosinophils in solid organ transplantation

Onyema

Guo

Hata

et al. 2020

American Journal of Transplantation

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Eosinophils are rare granulocytes that belong to the innate arm of the immune system. This cell population is traditionally defined as a destructive and cytotoxic mediator in asthma and helminth infection. Limited data in transplantation have suggested that eosinophils play a similar role in potentiating deleterious organ inflammation and immunologic rejection. Contrary to this long‐held notion, recent data have uncovered the possibility that eosinophils play an alternative role in immune homeostasis, defense against a wide range of pathogens, as well as downregulation of deleterious inflammation. Specifically, translational data from small animal models of lung transplantation have demonstrated a critical role for eosinophils in the downregulation of alloimmunity. These findings shed new light on the unique immunologic features of the lung allograft and demonstrate that environmental polarization may alter the phenotype and function of leukocyte populations previously thought to be static in nature. In this review, we provide an update on eosinophils in the homeostasis of the lung as well as other solid organs.

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Section: Eosinophils In Lung Transplantationcontrasting

confidence: 88%

Section: Eosinophils In Lung Transplantationsupporting

confidence: 81%

Section: Eosinophils In Lung Transplantationmentioning

confidence: 95%

Section: Eosinophils In Lung Transplantationmentioning

confidence: 99%

See 2 more Smart Citations

Deciphering the role of eosinophils in solid organ transplantation

Onyema

Guo

Hata

et al. 2020

American Journal of Transplantation

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“…In subsequent work, we identified graft-infiltrating eosinophils as the predominant producers of nitric oxide during tolerance induction 98. Most immunosuppressive regimens given to patients after lung transplantation have been adopted from studies in liver and kidney transplantation.…”

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confidence: 99%

The emerging role of regulatory T cells following lung transplantation

Gauthier

Harrison

Krupnick

et al. 2019

Immunological Reviews

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Regulatory T cells (Treg) have proven to be a powerful immunologic force in nearly every organ system and hold therapeutic potential for a wide range of diseases. Insights gained from non‐transplant pathologies, such as infection, cancer, and autoimmunity, are now being translated to the field of solid organ transplantation, particularly for livers and kidneys. Recent insights from animal models of lung transplantation have established that Tregs play a vital role in suppressing rejection and facilitating tolerance of lung allografts, and such discoveries are being validated in human studies and preclinical trials. Given that long‐term outcomes following lung transplantation remain profoundly limited by chronic rejection, Treg therapy holds the potential to significantly improve patient outcomes and should be aggressively investigated.

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