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. Author manuscript; available in PMC: 2021 Nov 1.
Published in final edited form as: Trends Immunol. 2020 Oct 7;41(11):1023–1036. doi: 10.1016/j.it.2020.09.002

Figure 2. Roles of Bhlhe40 and Bhlhe41 in murine tissue-resident immune cells.

Figure 2.

Bhlhe40 plays essential roles in tissue-resident macrophages (a) and lymphocytes (b), cooperating with Bhlhe41 in B1a cells and alveolar macrophages (AM) [39, 51, 57, 60]. In many cases, unknown tissue factors are thought to be important for Bhlhe40 expression, including retinoic acid [50]. These transcription factors regulate the proliferation of several resident leukocyte populations. In macrophages, this involves repression of c-Maf and MafB, but further mechanisms are thought to be involved [51, 57]. Recent work in TRM suggests that Bhlhe40 is also an important regulator of mitochondrial metabolism [60], though it is unclear whether Bhlhe40-deficient TRM are also deficient in proliferation. BM, bone marrow; Thio, thioglycolate; AM, alveolar macrophages; MDM, monocyte-derived macrophages; LPMs, large peritoneal macrophages; IL-4c, IL-4 cytokine complex; TILs, tumor-infiltrating lymphocytes; AcCoA, acetyl coenzyme A; RA, retinoic acid. This figure was created using BioRender (https://biorender.com/).