IL-23 promotes T cell trafficking in experimental autoimmune myocarditis

Area of Science:

• Immunology
• Cardiovascular Research
• Autoimmunity

Background:

• Th1 and Th17 cell-mediated autoimmunity are key drivers of myocarditis.
• Interleukin (IL)-12 and IL-23 from antigen-presenting cells (APCs) influence Th1 and Th17 differentiation.
• Experimental autoimmune myocarditis (EAM) serves as a model to study these mechanisms.

Purpose of the Study:

• To investigate the roles of IL-12 and IL-23 in CD4+ T cell responses within EAM.
• To elucidate the impact of IL-12 and IL-23 on T cell infiltration and inflammation in the heart.

Main Methods:

• Utilized cardiac self-antigen myosin heavy chain alpha (α-MyHC)-pulsed bone marrow-derived dendritic cells (bmDCs).
• Employed wild-type, IL-12p35-/-, and IL-23p19-/- mice and bmDCs in EAM models.
• Assessed T cell populations (CD4+, IFN-γ+, IL-17A+) and leukocyte infiltration (CD45+, CD3+) in cardiac tissue.

Main Results:

• Adoptive transfer of α-MyHC-pulsed IL-23p19-/- bmDCs reduced IL-17A+ CD4+ T cells and overall T lymphocyte infiltration in the heart.
• IL-12p35-/- bmDCs decreased IFN-γ-producing CD4+ T cells but did not impact T lymphocyte infiltration.
• Absence of IL-23 impaired T cell trafficking to the heart, as shown in IL-23p19-/- recipient mice and TCRMxIL-23p19-/- mice, with in vitro validation of IL-23's pro-migratory effect on CD4+ T cells.

Conclusions:

• IL-23 plays a critical, unique role in promoting T cell migration to the heart during autoimmune myocarditis.
• IL-23's pro-inflammatory activity in EAM is significantly linked to its ability to enhance T cell trafficking.
• Targeting IL-23 may offer a therapeutic strategy for autoimmune myocarditis by modulating T cell migration.