CD90 is not constitutively expressed in functional innate lymphoid cells

Abstract

Huge progress has been made in understanding the biology of innate lymphoid cells (ILC) by adopting several well-known concepts of T cell biology. As such flow cytometry gating strategies and markers, such as CD90, to identify ILC were discovered. Here we report that most non-NK intestinal ILC have a high expression of CD90 as expected, but surprisingly some have only a low or even no expression of this marker. CD90-negative CD127+ ILC were identified among all ILC subsets in the gut. CD90-negative cLP ILC2 were frequent at steady state. The frequency of CD90-negative CD127+ ILC was dependent on stimulatory cues in vitro and in vivo, and CD90-negative CD127+ ILC played a functional role as a source of IL-13, IFNγ and IL-17A at steady state and upon dextran sulphate sodium-elicited colitis. Hence, this study highlights for the first time that CD90 is not constitutively expressed by functional ILC in the gut.

Innate lymphoid cells—Underexplored guardians of immunity

“…The NK lineage commitment is initiated by Eomesodermin (Eomes), whereas ILC1 up-regulates T-bet instead, along with surface receptors such as IL-7Rα, CD90, CD49a, and CD200r1 [6,21,28,29] (Fig 1). Expression of these subset markers may differ depending on their microenvironment and activation state, often resulting in a rather blurred distinction between tissue-resident NK cells and ILC1s [3,[30][31][32]. Although NK cells and ILC1s diverge during development, some degree of plasticity may be maintained.…”

“…Current strategies rely on negative selection of ILCs, sorted by the lack of lineage-defining surface markers and by the expression of IL-7Rα, CD90, and CD49a [2,[92][93][94][95]. However, canonical ILC markers such as CD90 and IL-7R are subject to regulation and thus not constantly expressed on the surface of intestinal or pulmonary ILCs, respectively [31,32,96]. Moreover, the integrin CD49a may also show tissue-related variation [3,31].…”

Transcription factor-driven regulation of ILC1 and ILC3

“…In terms of lineage markers, the use of CD3 and a B cell marker, such as CD19, is the minimal requirement for detecting ILCs in mouse and human, but it is recommended and practiced in most studies reviewed here to use additional lineage markers targeting macrophages, neutrophils, granulocytes, and platelets. Some studies also use CD5 in the lineage cocktail [10][11][12][13][14][15][16][17][18][19][20][21][22][23]. However, the use of CD5 as a lineage marker is controversial because ILCs have been reported to express CD5, while CD5 + ILCs have also been shown to express αβTCR and have been related to nonfunctional T cells [2,24,25].…”

“…However, the use of CD5 as a lineage marker is controversial because ILCs have been reported to express CD5, while CD5 + ILCs have also been shown to express αβTCR and have been related to nonfunctional T cells [2,24,25]. Furthermore, CD127 is often used as a mouse and human ILC marker; however, CD127 expression in murine ILCs can be lost upon stimulation with IL7 [18][19][20][26][27][28][29][30][31][32][33][34][35]. Similarly, CD90 expression, in particular its high expression, has been used in a few studies to detect ILC3 [12,14,22,[36][37][38][39][40].…”

“…Similarly, CD90 expression, in particular its high expression, has been used in a few studies to detect ILC3 [12,14,22,[36][37][38][39][40]. However, preliminary data suggest that CD90 expression in ILCs is also lost in vitro and in vivo, and that ILC1 and ILC2 might have high expression of CD90 [18] (pers. commun.…”