Neutrophils Plasticity: The Regulatory Interface in Various Pathological Conditions

Abstract

It is now known that neutrophils make up a population of complex cells with great plasticity, challenging the old view of neutrophil association with tissue damage and early phases of infection. Here, we discuss different contexts in which these cells can induce anti-inflammatory responses. Although distinct surface markers and cytokines profiles were shown, the most reliable characterization of suppressor neutrophil subtypes relies on their functional characteristics. One important example of inhibitory neutrophils generation comes from in vivo treatment with G-CSF, for 5 days, as for hematopoieticstem-cell-transplantation (HSCT). In this case,donor blood is enriched in degranulated granulocytes harboring a functional regulatory phenotype, characterized by IL-10 production. These cells, when transferred together with HSCT, are able to reduce graft-versus-host-disease, being influenced by Treg cells and influencing them back. Importantly, this protection is long lasting and specific, keeping immunocompetence to other antigens. This regulation is paramount in HSCT, and represents a simple approach to be applied in humans. In summary, we discuss the interaction of neutrophils with other cell types and its consequence in immunomodulation. We believe these features confer an important bridge between innate and adaptive immune system, building a new knowledge for an underestimated cell type.

<p>The Binary Classification Of Chronic Diseases</p>

“…Corticosteroids are generally not effective in solid tumor malignancies, which are, as a whole, “high Treg” diseases 4. However, CS are very effective in treating lymphoid cancer, and were used as such for decades 101.…”

“…These pathologies are characterized by a lasting, weak effect of regulatory T cells (Treg). Under this condition, the immune system is not suppressed following its arousal (tumor associated neutrophils (TANs) of the N1 type are not switched to the N2 type, HDNs are not switched to LDNs, Th17 are continuously generated) and inflammation or auto-inflammation persist and may damage body tissues 4…”

“…A “high Treg” disease improves upon a decreased Treg activity, while a “low Treg” disease improves upon an increased Treg activity. Of note, an anti-inflammatory effect may be exerted by other types of cells, such as granulocytes4 or B cells 3. This article refers solely to the effect of regulatory T cells.…”

Neutrophil as a multifunctional relay in immune system

“…Однако некоторыми авторами было отмечено, что для реализации супрессорного и антипролиферативного эффекта необходима высокая концентрация H 2 O 2 , что, возможно, достигается большим скоплением нейтрофилов [111,167,193]. Кроме того H 2 O 2 нестабильна и может разрушаться эндогенными антиоксидантами, поэтому для ее влияния на Т-лимфоциты необходим тесный контакт между нейтрофилом и Т-клеткой [93,163]. В этой связи необходимо отметить, что в периферической крови людей с острым системным воспалением, индуцированным введением эндотоксина E. coli здоровым добровольцам или тяжелыми травмами, была идентифицирована субпопуляция зрелых нейтрофилов с фенотипом CD11c bright CD62L dim CD11b bright CD16 bright , способных подавлять пролиферацию Т-клеток in vitro.…”

“…Еще один механизм, опосредующий супрессорное влияние нейтрофилов на функцио нальную активность и пролиферацию Т-лимфоцитов, реализуется посредством прямого контакта между этими клетками через PD-L1-PD1 путь [163]. Рецептор PD1 (programmed cell death) экспрессируется в основном активированными Т-клетками.…”