Regulation of dendritic- and T-cell fate by injury-associated endogenous signals.
Two events characterize tissue injury and sterile inflammation: (1) generation/release of autoantigens, and (2) generation of homeostatic inflammatory signals. Homeostatic signals recruit leukocytes and promote cell migration and division to replace injured cells. Moreover, they activate antigen-presenting phagocytes, in particular, dendritic cells (DCs), in anticipation of microbial invasion. Activated DCs undergo a differentiation process, referred to as maturation, and migrate to secondary lymphoid organs. Maturing DCs upregulate the molecular machinery required for the priming of naive T cells, including T lymphocytes recognizing autoantigens, which represent a substantial fraction of the host T-cell repertoire. Recent data indicate that cues generated at sites of injury shape T-cell clonal expansion, regulating sensitivity to activation-dependent apoptosis and commitment towards a Th1, Th2, Th7, or regulatory T-cell fate. Endogenous signals of tissue injury, also called damage-associated molecular patterns (DAMPS) or alarmins, therefore provide a code for switching the outcome of the presentation of autoantigens towards results as diverse as T-cell-mcdiated protective immunity, tissue repair, persistent inflammation and autoimmunity, or tolerance.
Manfredi
Angelo A
AA
Vita-Salute San Raffaele University & San Raffaele Scientific Institute, 20132 Milano, Italy. manfredi.angelo@hsr.it
Capobianco
Annalisa
A
Bianchi
Marco E
ME
Rovere-Querini
Patrizia
P
D000818:Animals; D015551:Autoimmunity; D016923:Cell Death / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D024243:HMGB1 Protein / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014947:Wounds and Injuries / Q000276:immunology* / Q000378:metabolism
D024243:HMGB1 Protein