IL-23 promotes T cell trafficking in experimental autoimmune myocarditis

被引：0

作者：

Vdovenko, Daria ^{[1
]}

Stefanska, Monika ^{[2
]}

Wijnen, Winandus J. ^{[1
]}

Zarak-Crnkovic, Martina ^{[1
]}

Bachmann, Marta ^{[1
]}

Kania, Gabriela ^{[3
]}

Camici, Giovanni G. ^{[1
,4
]}

Luscher, Thomas F. ^{[1
,5
,6
]}

Eriksson, Urs ^{[1
]}

Blyszczuk, Przemyslaw ^{[1
,2
,3
]}

机构：

[1] Univ Zurich, Ctr Mol Cardiol, Schlieren, Switzerland

[2] Jagiellonian Univ, Med Coll, Dept Clin Immunol, Krakow, Poland

[3] Univ Zurich, Univ Hosp Zurich, Dept Rheumatol, Zurich, Switzerland

[4] Univ Hosp Zurich, Dept Res & Educ, Zurich, Switzerland

[5] Kings Coll London, Royal Brompton & Harefield Hosp, London, England

[6] Imperial Coll London, Royal Brompton & Harefield Hosp, London, England

来源：

JOURNAL OF IMMUNOLOGY | 2025年

关键词：

autoimmunity; migration; myocarditis; IL-23; T cell; DILATED CARDIOMYOPATHY; DENDRITIC CELLS; HEART-FAILURE; IFN-GAMMA; INTERLEUKIN-23; CYTOKINE; INFLAMMATION; COOPERATION; ROLES; IL-12;

D O I：

10.1093/jimmun/vkaf150

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Th1 and Th17 cell-mediated autoimmunity is critical for myocarditis induction. Antigen-presenting cell (APCs)-released interleukin (IL)-12 and IL-23 are implicated in the differentiation of Th1 and Th17 lineages. In this study, we utilized cardiac self-antigen myosin heavy chain alpha (alpha-MyHC)-pulsed bone marrow-derived dendritic cells (bmDCs) and wild-type, IL-12p35-/-, and IL-23p19-/- mice to investigate the influence of IL-12 and IL-23 on CD4+ T cells in experimental autoimmune myocarditis (EAM). All mice (Mus musculus) receiving alpha-MyHC-pulsed bmDCs developed acute myocarditis and accumulated interferon (IFN)-gamma-positive and IL-17A-positive CD4+ T cells in cardiac tissue. Compared to immunization with wild-type bmDCs, adoptive transfer of alpha-MyHC-pulsed IL-23p19-/- bmDCs resulted in decreased numbers of IL-17A+CD4+ T cells and in a twofold reduction of infiltrating T lymphocytes in the hearts of recipient mice, despite unaffected infiltration count of CD45+ leukocytes. In contrast, IL-12p35-/- bmDCs induced fewer IFN-gamma-producing CD4+ T cells but did not affect T lymphocyte infiltration. Furthermore, IL-23p19-/- recipient mice showed reduced heart-infiltrating CD3+ T cells, but not total CD45+, compared to wild-type mice after adoptive transfer of alpha-MyHC-pulsed IL-23p19-/- bmDCs. Likewise, in the transgenic TCRM model of EAM, TCRMxIL-23p19-/- mice showed reduced myocarditis severity and fewer T lymphocytes in their hearts pointing to impaired T cell trafficking in absence of IL-23. We validated the pro-migratory effect of IL-23 on activated CD4+ T cells in vitro and demonstrated an essential role of Rho GTPases in this process. Our findings provide new insights into the pro-inflammatory activity of IL-23 in autoimmune myocarditis, highlighting its unique role in promoting T cell migration.

引用

页数：11

共 49 条

[1] Interleukin-23 Drives Intestinal Inflammation through Direct Activity on T Cells [J].