Uterine fibroids (UF), also known as leiomyoma, is a benign uterine tumor with an unclear etiology that predominately affects the myometrium. Most of these monoclonal, estrogen-dependent uterine neoformations affect women in their reproductive years and 80% of them experience symptoms for the rest of their lives. Uterine fibroids can cause anemia from prolonged or heavy monthly flow, pelvic pain, or pressure, and difficulties in achieving successful pregnancies. UF develops as a result of changes of myometrial microenvironment under particular pathological circumstances [1].

It is unclear exactly what molecular and cellular alterations caused the UF to form and grow. UF are distinguished by an excessive buildup of extracellular matrix (ECM) elements like collagen, fibronectin, laminins, and proteoglycans. ECM deposition is thought to be the root of aberrant bleeding and pelvic pressure or pain [2]. ECM proteins induce mechanotransduction, a mechanism wherein increased tissue stiffness leads to bidirectional signaling via integrins and downstream mediators like Rho/p38 MAPK/ERK [3]. To control these tumors, it may be possible to prevent additional ECM formation and the associated fibrosis [4].

Additionally, uterine fibroids express proteolytic enzymes that are essential for ECM remodeling, such as matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). MMPs and other proteolytic enzymes release growth factors and activate numerous signal transduction pathways by destroying ECM components. Growth factors and steroid hormones control how much ECM accumulates and how it functions. Growth factors are bound and hidden by the ECM, which increases their stability and limits their activity. Among the suggested predisposing factors for ECM deposition is the shift in immune microenvironment from the proinflammatory type 1 immunity to the anti-inflammatory type 2 immunity [5].

Type 2 immunity is characterized, to some extent, as a counter-regulatory process controlling type 1 immunity and exhibits both host-protective and pathogenic qualities. Type 2 immunity promotes resolution of the inflammatory process after an injury. Chronic stimulation of type 2 response leads to tissue fibrosis [6]. The cytokines interleukin 4 (IL-4), IL-5, IL-9, and IL-13 are produced more frequently in type 2 immunity [7]. In this review, we highlight the involvement of type 2 immunosuppressive cells such as M2 macrophage, MDSCs, and Th17 in UF pathogenesis by affecting ECM accumulation