Low CD46 expression on activated CD4+ T cells predict improved Th1 cell reactivity to calcitriol in majority of patients with allergic eosinophilic asthma and healthy donors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F24%3A00080542" target="_blank" >RIV/00159816:_____/24:00080542 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/24:00137196 RIV/62156489:43110/24:43925708

Výsledek na webu

<a href="https://www.frontiersin.org/journals/allergy/articles/10.3389/falgy.2024.1462579/full" target="_blank" >https://www.frontiersin.org/journals/allergy/articles/10.3389/falgy.2024.1462579/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/falgy.2024.1462579" target="_blank" >10.3389/falgy.2024.1462579</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Low CD46 expression on activated CD4+ T cells predict improved Th1 cell reactivity to calcitriol in majority of patients with allergic eosinophilic asthma and healthy donors

Popis výsledku v původním jazyce

Background Previous research showed that the intracellular complement system, with CD46 as its central molecule, regulates the Th1 response associated with IFN-gamma production and transition to a type 1 regulatory response (Tr1) characterized by IL-10 production. This transition can be influenced by a vitamin D (calcitriol), favouring a shift towards Tr1 cells and increased IL-10 production, as described in some autoimmune diseases. Objective It is unknown whether calcitriol modulates CD46-induced Th1 response towards regulatory type 1 T cells (Tr1) in allergic eosinophilic asthma and its value in relation to reducing inflammatory response. Methods CD4(+) T cells from 58 patients with allergic eosinophilic asthma (AEA) and 49 healthy donors (HDs) were stimulated with alpha CD3/alpha CD46/IL-2 or alpha CD3/alpha CD46/IL-2/Calcitriol in vitro for 60 h and analyzed by flow cytometry. IFN-gamma and IL-10 levels in cell culture supernatants were measured using ELISA. Results CD4(+) T cells from patients with AEA demonstrated elevated CD46 expression in both the non-activated state and under stimulation conditions with alpha CD3/alpha CD46/IL-2 or alpha CD3/alpha CD46/IL-2/Calcitriol. Moreover, CD46 expression in AEA patients fluctuated with the pollen season, showing a significant increase during period of low pollen exposure. Calcitriol further induced CD4(+)Tr1 cells from in vitro generated CD4(+)Th1 cells in both HDs and AEA patients. However, in both cohorts were individuals (HDs: 35/49, AEA: 40/58) who responded to calcitriol with a more pronounced regulatory response. The calcitriol-induced regulatory effect manifested by a stronger surface decrease of CD46 on activated CD4+ T cells (by 40% in HDs and by 26% in AEA), accompanied by a significant inhibition of IFN-gamma and increased IL-10 production (by 31% in HDs and by 85% in AEA). These individuals were termed as the CD46D group. Contrary to this, calcitriol induced an increase in CD46 expression at the CD4(+) T cell surface in a minor group of HDs (14/49), and AEA patients (18/58), who were termed as the CD46I group. In CD46I group, CD4(+) T cells produced less IFN-gamma in comparison with CD46D group (by 33% in HDs and by 43% in AEA) and were unable to upregulate IL-10 production following stimulation with alpha CD3/alpha CD46/IL-2/Calcitriol. Conclusion Our results suggest the potential existence of a key for stratifying individuals suitable for calcitriol treatment in the context of low serum vitamin D levels. After validation in clinical studies, this key could be used as an adjunctive therapy not only for patients with allergic eosinophilic asthma, but also for other diseases.

Název v anglickém jazyce

Low CD46 expression on activated CD4+ T cells predict improved Th1 cell reactivity to calcitriol in majority of patients with allergic eosinophilic asthma and healthy donors

Popis výsledku anglicky

Background Previous research showed that the intracellular complement system, with CD46 as its central molecule, regulates the Th1 response associated with IFN-gamma production and transition to a type 1 regulatory response (Tr1) characterized by IL-10 production. This transition can be influenced by a vitamin D (calcitriol), favouring a shift towards Tr1 cells and increased IL-10 production, as described in some autoimmune diseases. Objective It is unknown whether calcitriol modulates CD46-induced Th1 response towards regulatory type 1 T cells (Tr1) in allergic eosinophilic asthma and its value in relation to reducing inflammatory response. Methods CD4(+) T cells from 58 patients with allergic eosinophilic asthma (AEA) and 49 healthy donors (HDs) were stimulated with alpha CD3/alpha CD46/IL-2 or alpha CD3/alpha CD46/IL-2/Calcitriol in vitro for 60 h and analyzed by flow cytometry. IFN-gamma and IL-10 levels in cell culture supernatants were measured using ELISA. Results CD4(+) T cells from patients with AEA demonstrated elevated CD46 expression in both the non-activated state and under stimulation conditions with alpha CD3/alpha CD46/IL-2 or alpha CD3/alpha CD46/IL-2/Calcitriol. Moreover, CD46 expression in AEA patients fluctuated with the pollen season, showing a significant increase during period of low pollen exposure. Calcitriol further induced CD4(+)Tr1 cells from in vitro generated CD4(+)Th1 cells in both HDs and AEA patients. However, in both cohorts were individuals (HDs: 35/49, AEA: 40/58) who responded to calcitriol with a more pronounced regulatory response. The calcitriol-induced regulatory effect manifested by a stronger surface decrease of CD46 on activated CD4+ T cells (by 40% in HDs and by 26% in AEA), accompanied by a significant inhibition of IFN-gamma and increased IL-10 production (by 31% in HDs and by 85% in AEA). These individuals were termed as the CD46D group. Contrary to this, calcitriol induced an increase in CD46 expression at the CD4(+) T cell surface in a minor group of HDs (14/49), and AEA patients (18/58), who were termed as the CD46I group. In CD46I group, CD4(+) T cells produced less IFN-gamma in comparison with CD46D group (by 33% in HDs and by 43% in AEA) and were unable to upregulate IL-10 production following stimulation with alpha CD3/alpha CD46/IL-2/Calcitriol. Conclusion Our results suggest the potential existence of a key for stratifying individuals suitable for calcitriol treatment in the context of low serum vitamin D levels. After validation in clinical studies, this key could be used as an adjunctive therapy not only for patients with allergic eosinophilic asthma, but also for other diseases.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30225 - Allergy

Projekt

<a href="/cs/project/NU20-05-00146" target="_blank" >NU20-05-00146: Změny intracelulárního komplementu u pacientů s alergickým eozinofilním astmatem</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Frontiers in Allergy

ISSN

2673-6101

e-ISSN

2673-6101

Svazek periodika

5

Číslo periodika v rámci svazku

2024

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

18

Strana od-do

1462579

Kód UT WoS článku

001330400600001

EID výsledku v databázi Scopus

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