TY - JOUR
T1 - The expansion in lymphoid organs of IL-4+ BATF+ T follicular helper cells is linked to IgG4 class switching in vivo
AU - Maehara, Takashi
AU - Mattoo, Hamid
AU - Mahajan, Vinay S.
AU - Murphy, Samuel J.H.
AU - Yuen, Grace J.
AU - Ishiguro, Noriko
AU - Ohta, Miho
AU - Moriyama, Masafumi
AU - Saeki, Takako
AU - Yamamoto, Hidetaka
AU - Yamauchi, Masaki
AU - Daccache, Joe
AU - Kiyoshima, Tamotsu
AU - Nakamura, Seiji
AU - Stone, John H.
AU - Pillai, Shiv
N1 - Funding Information:
This work was supported by awards AI110495 (to S Pillai) and AI113163 (to VS Mahajan) from the National Institute of Health and supported by the Japanese Society for the Promotion of Science Postdoctoral Fellowships for Research Abroad to T Maehara and Mochida Memorial Medical and Pharmaceutical Foundation to T Maehara. The authors thank Eric Safai for help with the collection and processing of samples from Massachusetts General Hospital and Thomas Diefenbach of the Imaging Core at the Ragon Institute for help and advice.
Publisher Copyright:
© 2018 Maehara et al.
PY - 2018
Y1 - 2018
N2 - Distinct T follicular helper (TFH) subsets that influence specific class-switching events are assumed to exist, but the accumulation of isotype-specific TFH subsets in secondary lymphoid organs (SLOs) and tertiary lymphoid organs has not been hitherto demonstrated. IL-4–expressing TFH cells are surprisingly sparse in human SLOs. In contrast, in IgG4-related disease (IgG4-RD), a disorder characterized by polarized Ig class switching, most TFH cells in tertiary and SLOs make IL-4. Human IL-4+ TFH cells do not express GATA-3 but express nuclear BATF, and the transcriptomes of IL-4–secreting TFH cells differ from both PD1hi TFH cells that do not secrete IL-4 and IL-4–secreting non-TFH cells. Unlike IgG4-RD, IL-4+ TFH cells are rarely found in tertiary lymphoid organs in Sjögren’s syndrome, a disorder in which IgG4 is not elevated. The proportion of CD4+IL-4+BATF+ T cells and CD4+IL-4+CXCR5+ T cells in IgG4-RD tissues correlates tightly with tissue IgG4 plasma cell numbers and plasma IgG4 levels in patients but not with the total plasma levels of other isotypes. These data describe a disease-related TFH subpopulation in human tertiary lymphoid organs and SLOs that is linked to IgG4 class switching.
AB - Distinct T follicular helper (TFH) subsets that influence specific class-switching events are assumed to exist, but the accumulation of isotype-specific TFH subsets in secondary lymphoid organs (SLOs) and tertiary lymphoid organs has not been hitherto demonstrated. IL-4–expressing TFH cells are surprisingly sparse in human SLOs. In contrast, in IgG4-related disease (IgG4-RD), a disorder characterized by polarized Ig class switching, most TFH cells in tertiary and SLOs make IL-4. Human IL-4+ TFH cells do not express GATA-3 but express nuclear BATF, and the transcriptomes of IL-4–secreting TFH cells differ from both PD1hi TFH cells that do not secrete IL-4 and IL-4–secreting non-TFH cells. Unlike IgG4-RD, IL-4+ TFH cells are rarely found in tertiary lymphoid organs in Sjögren’s syndrome, a disorder in which IgG4 is not elevated. The proportion of CD4+IL-4+BATF+ T cells and CD4+IL-4+CXCR5+ T cells in IgG4-RD tissues correlates tightly with tissue IgG4 plasma cell numbers and plasma IgG4 levels in patients but not with the total plasma levels of other isotypes. These data describe a disease-related TFH subpopulation in human tertiary lymphoid organs and SLOs that is linked to IgG4 class switching.
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U2 - 10.26508/lsa.201800050
DO - 10.26508/lsa.201800050
M3 - Article
C2 - 29984361
AN - SCOPUS:85057038132
SN - 2575-1077
VL - 1
JO - Life Science Alliance
JF - Life Science Alliance
IS - 1
M1 - e201800050
ER -
