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Tissue Remodeling and Repair During Type 2 Inflammation

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The Th2 Type Immune Response in Health and Disease

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Abstract

Tissue remodeling and repair following injury is an active immunologic and tissue regenerative process predicated upon a T helper type 2 (Th2) cell response. While typically associated with immunity to helminths or allergic inflammation, the Th2 response mediates tissue repair, acting to regulate inflammation while promoting the expression of wound healing genes and growth factors involved in tissue regeneration. However, if not appropriately regulated, Th2 responses can drive fibrosis, a pathologic condition where excess extracellular matrix and scar tissue are formed to fill the wound instead of newly regenerated tissue. In this chapter, we review how the Th2 immune responses are generated following injury, and the mechanism by which Th2 cytokines orchestrate wound healing. We focus on the immune cells (e.g., Th2 cells and alternatively activated macrophages) that direct this complex process, and the cytokines (e.g., IL-4 and IL-13) and growth factors (e.g., TGF-β) they secrete to mediate wound healing. Second, we detail the downstream wound healing pathways triggered by these factors notably tissue remodeling, extracellular matrix deposition and tissue regeneration. Finally, we discuss the clinical implications of the Th2 immune response on wound healing and fibrosis, and what key factors can be targeted to regulate the balance between optimal wound healing and detrimental fibrosis.

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Abbreviations

AAM:

Alternatively activated macrophage

CAM:

Classically activated macrophage

DTR:

Diphtheria toxin receptor

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

FAP:

Fibro/adipogenic progenitor

FGF:

Fibroblast growth factor

IGF:

Insulin-like growth factor-1

ILC:

Innate lymphoid cell

LAP:

Latency associated protein

MMP:

Matrix metalloproteinase

MSC:

Mesenchymal stem cell

RELM:

Resistin-like molecule

PDGF:

Platelet-derived growth factor

TGF-β:

Transforming growth factor β

TIMP:

Tissue inhibitor of metalloproteinase

Th:

T helper

TREM2:

Triggering receptor expressed on myeloid cell 2

TSLP:

Thymic stromal lymphopoietin

VEGF:

Vascular endothelial growth factor

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    Authors and Affiliations

    1. Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA, USA

      Alexander J. Chan, Jessica C. Jang & Meera G. Nair

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    1. Alexander J. Chan
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    2. Jessica C. Jang
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    3. Meera G. Nair
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    Correspondence to Meera G. Nair .

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    Editors and Affiliations

    1. Rutgers, The State University of New Jer , NEWARK, New Jersey, USA

      William C. Gause

    2. Department of Microbiology and Immunology Belfer Research Building, Michael Kors Professor of Immunology; Director, Jill Roberts Institute for Research in Inflammatory Bowel Disease; Weill Cornell Medical College; Cornell University; Joan and Sanford I. Weill Department of Medicine, New York, New York, USA

      David Artis

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    Chan, A.J., Jang, J.C., Nair, M.G. (2016). Tissue Remodeling and Repair During Type 2 Inflammation. In: Gause, W., Artis, D. (eds) The Th2 Type Immune Response in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2911-5_7

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